A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth
Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcripti...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Lin, Chuwen [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
|---|
| Schlagwörter: |
|---|
| Umfang: |
13 |
|---|
| Übergeordnetes Werk: |
Enthalten in: 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY - 2011, Amsterdam [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:403 ; year:2015 ; number:1 ; day:1 ; month:07 ; pages:101-113 ; extent:13 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ydbio.2015.04.014 |
|---|
| Katalog-ID: |
ELV034890386 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV034890386 | ||
| 003 | DE-627 | ||
| 005 | 20230625202240.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180603s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ydbio.2015.04.014 |2 doi | |
| 028 | 5 | 2 | |a GBVA2015021000001.pica |
| 035 | |a (DE-627)ELV034890386 | ||
| 035 | |a (ELSEVIER)S0012-1606(15)00214-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 | |
| 082 | 0 | 4 | |a 570 |q DE-600 |
| 082 | 0 | 4 | |a 610 |q VZ |
| 082 | 0 | 4 | |a 570 |a 540 |q VZ |
| 100 | 1 | |a Lin, Chuwen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| 264 | 1 | |c 2015transfer abstract | |
| 300 | |a 13 | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. | ||
| 520 | |a Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. | ||
| 650 | 7 | |a Hippo signaling |2 Elsevier | |
| 650 | 7 | |a Lung |2 Elsevier | |
| 650 | 7 | |a Development |2 Elsevier | |
| 650 | 7 | |a Mst1/2 |2 Elsevier | |
| 650 | 7 | |a Yap |2 Elsevier | |
| 700 | 1 | |a Yao, Erica |4 oth | |
| 700 | 1 | |a Chuang, Pao-Tien |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |t 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |d 2011 |g Amsterdam [u.a.] |w (DE-627)ELV010652000 |
| 773 | 1 | 8 | |g volume:403 |g year:2015 |g number:1 |g day:1 |g month:07 |g pages:101-113 |g extent:13 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ydbio.2015.04.014 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_147 | ||
| 912 | |a GBV_ILN_2018 | ||
| 912 | |a GBV_ILN_2034 | ||
| 951 | |a AR | ||
| 952 | |d 403 |j 2015 |e 1 |b 1 |c 0701 |h 101-113 |g 13 | ||
| 953 | |2 045F |a 570 | ||
| author_variant |
c l cl |
|---|---|
| matchkey_str |
linchuwenyaoericachuangpaotien:2015----:cnevds1ypxseitsipsgaig |
| hierarchy_sort_str |
2015transfer abstract |
| publishDate |
2015 |
| allfields |
10.1016/j.ydbio.2015.04.014 doi GBVA2015021000001.pica (DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Lin, Chuwen verfasserin aut A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth 2015transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier Yao, Erica oth Chuang, Pao-Tien oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 https://doi.org/10.1016/j.ydbio.2015.04.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 403 2015 1 1 0701 101-113 13 045F 570 |
| spelling |
10.1016/j.ydbio.2015.04.014 doi GBVA2015021000001.pica (DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Lin, Chuwen verfasserin aut A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth 2015transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier Yao, Erica oth Chuang, Pao-Tien oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 https://doi.org/10.1016/j.ydbio.2015.04.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 403 2015 1 1 0701 101-113 13 045F 570 |
| allfields_unstemmed |
10.1016/j.ydbio.2015.04.014 doi GBVA2015021000001.pica (DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Lin, Chuwen verfasserin aut A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth 2015transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier Yao, Erica oth Chuang, Pao-Tien oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 https://doi.org/10.1016/j.ydbio.2015.04.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 403 2015 1 1 0701 101-113 13 045F 570 |
| allfieldsGer |
10.1016/j.ydbio.2015.04.014 doi GBVA2015021000001.pica (DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Lin, Chuwen verfasserin aut A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth 2015transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier Yao, Erica oth Chuang, Pao-Tien oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 https://doi.org/10.1016/j.ydbio.2015.04.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 403 2015 1 1 0701 101-113 13 045F 570 |
| allfieldsSound |
10.1016/j.ydbio.2015.04.014 doi GBVA2015021000001.pica (DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Lin, Chuwen verfasserin aut A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth 2015transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier Yao, Erica oth Chuang, Pao-Tien oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 https://doi.org/10.1016/j.ydbio.2015.04.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 403 2015 1 1 0701 101-113 13 045F 570 |
| language |
English |
| source |
Enthalten in 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY Amsterdam [u.a.] volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 |
| sourceStr |
Enthalten in 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY Amsterdam [u.a.] volume:403 year:2015 number:1 day:1 month:07 pages:101-113 extent:13 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Hippo signaling Lung Development Mst1/2 Yap |
| dewey-raw |
570 |
| isfreeaccess_bool |
false |
| container_title |
326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |
| authorswithroles_txt_mv |
Lin, Chuwen @@aut@@ Yao, Erica @@oth@@ Chuang, Pao-Tien @@oth@@ |
| publishDateDaySort_date |
2015-01-01T00:00:00Z |
| hierarchy_top_id |
ELV010652000 |
| dewey-sort |
3570 |
| id |
ELV034890386 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV034890386</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625202240.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2015 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ydbio.2015.04.014</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2015021000001.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV034890386</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0012-1606(15)00214-6</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">570</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="a">540</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lin, Chuwen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">13</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Hippo signaling</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Lung</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Development</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Mst1/2</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Yap</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yao, Erica</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chuang, Pao-Tien</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="t">326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY</subfield><subfield code="d">2011</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV010652000</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:403</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:1</subfield><subfield code="g">day:1</subfield><subfield code="g">month:07</subfield><subfield code="g">pages:101-113</subfield><subfield code="g">extent:13</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ydbio.2015.04.014</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_147</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2018</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">403</subfield><subfield code="j">2015</subfield><subfield code="e">1</subfield><subfield code="b">1</subfield><subfield code="c">0701</subfield><subfield code="h">101-113</subfield><subfield code="g">13</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">570</subfield></datafield></record></collection>
|
| author |
Lin, Chuwen |
| spellingShingle |
Lin, Chuwen ddc 570 ddc 610 Elsevier Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| authorStr |
Lin, Chuwen |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV010652000 |
| format |
electronic Article |
| dewey-ones |
570 - Life sciences; biology 610 - Medicine & health 540 - Chemistry & allied sciences |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
570 570 DE-600 610 VZ 570 540 VZ A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap Elsevier |
| topic |
ddc 570 ddc 610 Elsevier Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap |
| topic_unstemmed |
ddc 570 ddc 610 Elsevier Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap |
| topic_browse |
ddc 570 ddc 610 Elsevier Hippo signaling Elsevier Lung Elsevier Development Elsevier Mst1/2 Elsevier Yap |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
e y ey p t c ptc |
| hierarchy_parent_title |
326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |
| hierarchy_parent_id |
ELV010652000 |
| dewey-tens |
570 - Life sciences; biology 610 - Medicine & health 540 - Chemistry |
| hierarchy_top_title |
326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV010652000 |
| title |
A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| ctrlnum |
(DE-627)ELV034890386 (ELSEVIER)S0012-1606(15)00214-6 |
| title_full |
A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| author_sort |
Lin, Chuwen |
| journal |
326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |
| journalStr |
326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
500 - Science 600 - Technology |
| recordtype |
marc |
| publishDateSort |
2015 |
| contenttype_str_mv |
zzz |
| container_start_page |
101 |
| author_browse |
Lin, Chuwen |
| container_volume |
403 |
| physical |
13 |
| class |
570 570 DE-600 610 VZ 570 540 VZ |
| format_se |
Elektronische Aufsätze |
| author-letter |
Lin, Chuwen |
| doi_str_mv |
10.1016/j.ydbio.2015.04.014 |
| dewey-full |
570 610 540 |
| title_sort |
a conserved mst1/2–yap axis mediates hippo signaling during lung growth |
| title_auth |
A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| abstract |
Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. |
| abstractGer |
Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. |
| abstract_unstemmed |
Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development. |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 |
| container_issue |
1 |
| title_short |
A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth |
| url |
https://doi.org/10.1016/j.ydbio.2015.04.014 |
| remote_bool |
true |
| author2 |
Yao, Erica Chuang, Pao-Tien |
| author2Str |
Yao, Erica Chuang, Pao-Tien |
| ppnlink |
ELV010652000 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth |
| doi_str |
10.1016/j.ydbio.2015.04.014 |
| up_date |
2024-07-06T22:15:04.805Z |
| _version_ |
1803869597001056256 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV034890386</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625202240.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2015 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ydbio.2015.04.014</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2015021000001.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV034890386</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0012-1606(15)00214-6</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">570</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="a">540</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lin, Chuwen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">13</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2–YAP axis in coordinating lung growth during development.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Hippo signaling</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Lung</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Development</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Mst1/2</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Yap</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yao, Erica</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chuang, Pao-Tien</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="t">326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY</subfield><subfield code="d">2011</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV010652000</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:403</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:1</subfield><subfield code="g">day:1</subfield><subfield code="g">month:07</subfield><subfield code="g">pages:101-113</subfield><subfield code="g">extent:13</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ydbio.2015.04.014</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_147</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2018</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">403</subfield><subfield code="j">2015</subfield><subfield code="e">1</subfield><subfield code="b">1</subfield><subfield code="c">0701</subfield><subfield code="h">101-113</subfield><subfield code="g">13</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">570</subfield></datafield></record></collection>
|
| score |
7.3992214 |