Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins
mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Iacovelli, L. [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2014transfer abstract |
|---|
| Schlagwörter: |
|---|
| Umfang: |
10 |
|---|
| Übergeordnetes Werk: |
Enthalten in: Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes - March, Brayden ELSEVIER, 2023, Amsterdam [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:77 ; year:2014 ; pages:303-312 ; extent:10 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.neuropharm.2013.10.013 |
|---|
| Katalog-ID: |
ELV023153997 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV023153997 | ||
| 003 | DE-627 | ||
| 005 | 20230625140824.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180603s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.neuropharm.2013.10.013 |2 doi | |
| 028 | 5 | 2 | |a GBVA2014022000014.pica |
| 035 | |a (DE-627)ELV023153997 | ||
| 035 | |a (ELSEVIER)S0028-3908(13)00487-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 610 | |
| 082 | 0 | 4 | |a 610 |q DE-600 |
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.88 |2 bkl | ||
| 100 | 1 | |a Iacovelli, L. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| 264 | 1 | |c 2014transfer abstract | |
| 300 | |a 10 | ||
| 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 mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. | ||
| 520 | |a mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. | ||
| 650 | 7 | |a mGlu7 receptors |2 Elsevier | |
| 650 | 7 | |a GRK |2 Elsevier | |
| 650 | 7 | |a Signaling regulation |2 Elsevier | |
| 650 | 7 | |a MAP kinases |2 Elsevier | |
| 650 | 7 | |a Arrestins |2 Elsevier | |
| 650 | 7 | |a Jun kinases |2 Elsevier | |
| 700 | 1 | |a Felicioni, M. |4 oth | |
| 700 | 1 | |a Nisticò, R. |4 oth | |
| 700 | 1 | |a Nicoletti, F. |4 oth | |
| 700 | 1 | |a De Blasi, A. |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier Science |a March, Brayden ELSEVIER |t Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |d 2023 |g Amsterdam [u.a.] |w (DE-627)ELV009446303 |
| 773 | 1 | 8 | |g volume:77 |g year:2014 |g pages:303-312 |g extent:10 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.neuropharm.2013.10.013 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 912 | |a SSG-OLC-PHA | ||
| 936 | b | k | |a 44.88 |j Urologie |j Nephrologie |q VZ |
| 951 | |a AR | ||
| 952 | |d 77 |j 2014 |h 303-312 |g 10 | ||
| 953 | |2 045F |a 610 | ||
| author_variant |
l i li |
|---|---|
| matchkey_str |
iacovellilfelicionimnisticrnicolettifdeb:2014----:eetvrgltoorcmiatyxrseml7eaorpcltmtrcposypoeno |
| hierarchy_sort_str |
2014transfer abstract |
| bklnumber |
44.88 |
| publishDate |
2014 |
| allfields |
10.1016/j.neuropharm.2013.10.013 doi GBVA2014022000014.pica (DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.88 bkl Iacovelli, L. verfasserin aut Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins 2014transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier Felicioni, M. oth Nisticò, R. oth Nicoletti, F. oth De Blasi, A. oth Enthalten in Elsevier Science March, Brayden ELSEVIER Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes 2023 Amsterdam [u.a.] (DE-627)ELV009446303 volume:77 year:2014 pages:303-312 extent:10 https://doi.org/10.1016/j.neuropharm.2013.10.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.88 Urologie Nephrologie VZ AR 77 2014 303-312 10 045F 610 |
| spelling |
10.1016/j.neuropharm.2013.10.013 doi GBVA2014022000014.pica (DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.88 bkl Iacovelli, L. verfasserin aut Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins 2014transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier Felicioni, M. oth Nisticò, R. oth Nicoletti, F. oth De Blasi, A. oth Enthalten in Elsevier Science March, Brayden ELSEVIER Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes 2023 Amsterdam [u.a.] (DE-627)ELV009446303 volume:77 year:2014 pages:303-312 extent:10 https://doi.org/10.1016/j.neuropharm.2013.10.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.88 Urologie Nephrologie VZ AR 77 2014 303-312 10 045F 610 |
| allfields_unstemmed |
10.1016/j.neuropharm.2013.10.013 doi GBVA2014022000014.pica (DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.88 bkl Iacovelli, L. verfasserin aut Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins 2014transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier Felicioni, M. oth Nisticò, R. oth Nicoletti, F. oth De Blasi, A. oth Enthalten in Elsevier Science March, Brayden ELSEVIER Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes 2023 Amsterdam [u.a.] (DE-627)ELV009446303 volume:77 year:2014 pages:303-312 extent:10 https://doi.org/10.1016/j.neuropharm.2013.10.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.88 Urologie Nephrologie VZ AR 77 2014 303-312 10 045F 610 |
| allfieldsGer |
10.1016/j.neuropharm.2013.10.013 doi GBVA2014022000014.pica (DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.88 bkl Iacovelli, L. verfasserin aut Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins 2014transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier Felicioni, M. oth Nisticò, R. oth Nicoletti, F. oth De Blasi, A. oth Enthalten in Elsevier Science March, Brayden ELSEVIER Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes 2023 Amsterdam [u.a.] (DE-627)ELV009446303 volume:77 year:2014 pages:303-312 extent:10 https://doi.org/10.1016/j.neuropharm.2013.10.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.88 Urologie Nephrologie VZ AR 77 2014 303-312 10 045F 610 |
| allfieldsSound |
10.1016/j.neuropharm.2013.10.013 doi GBVA2014022000014.pica (DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.88 bkl Iacovelli, L. verfasserin aut Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins 2014transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier Felicioni, M. oth Nisticò, R. oth Nicoletti, F. oth De Blasi, A. oth Enthalten in Elsevier Science March, Brayden ELSEVIER Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes 2023 Amsterdam [u.a.] (DE-627)ELV009446303 volume:77 year:2014 pages:303-312 extent:10 https://doi.org/10.1016/j.neuropharm.2013.10.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.88 Urologie Nephrologie VZ AR 77 2014 303-312 10 045F 610 |
| language |
English |
| source |
Enthalten in Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes Amsterdam [u.a.] volume:77 year:2014 pages:303-312 extent:10 |
| sourceStr |
Enthalten in Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes Amsterdam [u.a.] volume:77 year:2014 pages:303-312 extent:10 |
| format_phy_str_mv |
Article |
| bklname |
Urologie Nephrologie |
| institution |
findex.gbv.de |
| topic_facet |
mGlu7 receptors GRK Signaling regulation MAP kinases Arrestins Jun kinases |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |
| authorswithroles_txt_mv |
Iacovelli, L. @@aut@@ Felicioni, M. @@oth@@ Nisticò, R. @@oth@@ Nicoletti, F. @@oth@@ De Blasi, A. @@oth@@ |
| publishDateDaySort_date |
2014-01-01T00:00:00Z |
| hierarchy_top_id |
ELV009446303 |
| dewey-sort |
3610 |
| id |
ELV023153997 |
| 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">ELV023153997</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625140824.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2014 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.neuropharm.2013.10.013</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2014022000014.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV023153997</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0028-3908(13)00487-5</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">610</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</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="084" ind1=" " ind2=" "><subfield code="a">44.88</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Iacovelli, L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">10</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">mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">mGlu7 receptors</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">GRK</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Signaling regulation</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MAP kinases</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Arrestins</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Jun kinases</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Felicioni, M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nisticò, R.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nicoletti, F.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">De Blasi, A.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier Science</subfield><subfield code="a">March, Brayden ELSEVIER</subfield><subfield code="t">Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes</subfield><subfield code="d">2023</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV009446303</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:77</subfield><subfield code="g">year:2014</subfield><subfield code="g">pages:303-312</subfield><subfield code="g">extent:10</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.neuropharm.2013.10.013</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="936" ind1="b" ind2="k"><subfield code="a">44.88</subfield><subfield code="j">Urologie</subfield><subfield code="j">Nephrologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">77</subfield><subfield code="j">2014</subfield><subfield code="h">303-312</subfield><subfield code="g">10</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">610</subfield></datafield></record></collection>
|
| author |
Iacovelli, L. |
| spellingShingle |
Iacovelli, L. ddc 610 bkl 44.88 Elsevier mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| authorStr |
Iacovelli, L. |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV009446303 |
| format |
electronic Article |
| dewey-ones |
610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
610 610 DE-600 610 VZ 44.88 bkl Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases Elsevier |
| topic |
ddc 610 bkl 44.88 Elsevier mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases |
| topic_unstemmed |
ddc 610 bkl 44.88 Elsevier mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases |
| topic_browse |
ddc 610 bkl 44.88 Elsevier mGlu7 receptors Elsevier GRK Elsevier Signaling regulation Elsevier MAP kinases Elsevier Arrestins Elsevier Jun kinases |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
m f mf r n rn f n fn b a d ba bad |
| hierarchy_parent_title |
Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |
| hierarchy_parent_id |
ELV009446303 |
| dewey-tens |
610 - Medicine & health |
| hierarchy_top_title |
Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV009446303 |
| title |
Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| ctrlnum |
(DE-627)ELV023153997 (ELSEVIER)S0028-3908(13)00487-5 |
| title_full |
Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| author_sort |
Iacovelli, L. |
| journal |
Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |
| journalStr |
Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2014 |
| contenttype_str_mv |
zzz |
| container_start_page |
303 |
| author_browse |
Iacovelli, L. |
| container_volume |
77 |
| physical |
10 |
| class |
610 610 DE-600 610 VZ 44.88 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
Iacovelli, L. |
| doi_str_mv |
10.1016/j.neuropharm.2013.10.013 |
| dewey-full |
610 |
| title_sort |
selective regulation of recombinantly expressed mglu7 metabotropic glutamate receptors by g protein-coupled receptor kinases and arrestins |
| title_auth |
Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| abstract |
mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. |
| abstractGer |
mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. |
| abstract_unstemmed |
mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA |
| title_short |
Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins |
| url |
https://doi.org/10.1016/j.neuropharm.2013.10.013 |
| remote_bool |
true |
| author2 |
Felicioni, M. Nisticò, R. Nicoletti, F. De Blasi, A. |
| author2Str |
Felicioni, M. Nisticò, R. Nicoletti, F. De Blasi, A. |
| ppnlink |
ELV009446303 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth |
| doi_str |
10.1016/j.neuropharm.2013.10.013 |
| up_date |
2024-07-06T18:08:19.440Z |
| _version_ |
1803854072450646016 |
| 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">ELV023153997</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625140824.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180603s2014 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.neuropharm.2013.10.013</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBVA2014022000014.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV023153997</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0028-3908(13)00487-5</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">610</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</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="084" ind1=" " ind2=" "><subfield code="a">44.88</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Iacovelli, L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Selective regulation of recombinantly expressed mGlu7 metabotropic glutamate receptors by G protein-coupled receptor kinases and arrestins</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">10</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">mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">mGlu7 receptors</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">GRK</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Signaling regulation</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MAP kinases</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Arrestins</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Jun kinases</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Felicioni, M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nisticò, R.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nicoletti, F.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">De Blasi, A.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier Science</subfield><subfield code="a">March, Brayden ELSEVIER</subfield><subfield code="t">Phallus Preservation for Locally Advanced Proximal Primary Urethral Carcinoma: Technique and Outcomes</subfield><subfield code="d">2023</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV009446303</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:77</subfield><subfield code="g">year:2014</subfield><subfield code="g">pages:303-312</subfield><subfield code="g">extent:10</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.neuropharm.2013.10.013</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="936" ind1="b" ind2="k"><subfield code="a">44.88</subfield><subfield code="j">Urologie</subfield><subfield code="j">Nephrologie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">77</subfield><subfield code="j">2014</subfield><subfield code="h">303-312</subfield><subfield code="g">10</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">610</subfield></datafield></record></collection>
|
| score |
7.3999777 |