Systems level expression correlation of Ras GTPase regulators

Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality...
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Autor*in:	E. Besray Unal [verfasserIn] Christina Kiel [verfasserIn] Hannah Benisty [verfasserIn] Andrew Campbell [verfasserIn] Karen Pickering [verfasserIn] Nils Blüthgen [verfasserIn] Owen J. Sansom [verfasserIn] Luis Serrano [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors

Übergeordnetes Werk:	In: Cell Communication and Signaling - BMC, 2004, 16(2018), 1, Seite 12
Übergeordnetes Werk:	volume:16 ; year:2018 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12964-018-0256-8

Katalog-ID:	DOAJ031413129

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520			\|a Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
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allfields	10.1186/s12964-018-0256-8 doi (DE-627)DOAJ031413129 (DE-599)DOAJaf1884eb1e0a43b986d6bddbbd3ed46a DE-627 ger DE-627 rakwb eng QH573-671 E. Besray Unal verfasserin aut Systems level expression correlation of Ras GTPase regulators 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein. Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology Christina Kiel verfasserin aut Hannah Benisty verfasserin aut Andrew Campbell verfasserin aut Karen Pickering verfasserin aut Nils Blüthgen verfasserin aut Owen J. Sansom verfasserin aut Luis Serrano verfasserin aut In Cell Communication and Signaling BMC, 2004 16(2018), 1, Seite 12 (DE-627)37375275X (DE-600)2126315-2 1478811X nnns volume:16 year:2018 number:1 pages:12 https://doi.org/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a kostenfrei http://link.springer.com/article/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/toc/1478-811X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2018 1 12
spelling	10.1186/s12964-018-0256-8 doi (DE-627)DOAJ031413129 (DE-599)DOAJaf1884eb1e0a43b986d6bddbbd3ed46a DE-627 ger DE-627 rakwb eng QH573-671 E. Besray Unal verfasserin aut Systems level expression correlation of Ras GTPase regulators 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein. Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology Christina Kiel verfasserin aut Hannah Benisty verfasserin aut Andrew Campbell verfasserin aut Karen Pickering verfasserin aut Nils Blüthgen verfasserin aut Owen J. Sansom verfasserin aut Luis Serrano verfasserin aut In Cell Communication and Signaling BMC, 2004 16(2018), 1, Seite 12 (DE-627)37375275X (DE-600)2126315-2 1478811X nnns volume:16 year:2018 number:1 pages:12 https://doi.org/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a kostenfrei http://link.springer.com/article/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/toc/1478-811X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2018 1 12
allfields_unstemmed	10.1186/s12964-018-0256-8 doi (DE-627)DOAJ031413129 (DE-599)DOAJaf1884eb1e0a43b986d6bddbbd3ed46a DE-627 ger DE-627 rakwb eng QH573-671 E. Besray Unal verfasserin aut Systems level expression correlation of Ras GTPase regulators 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein. Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology Christina Kiel verfasserin aut Hannah Benisty verfasserin aut Andrew Campbell verfasserin aut Karen Pickering verfasserin aut Nils Blüthgen verfasserin aut Owen J. Sansom verfasserin aut Luis Serrano verfasserin aut In Cell Communication and Signaling BMC, 2004 16(2018), 1, Seite 12 (DE-627)37375275X (DE-600)2126315-2 1478811X nnns volume:16 year:2018 number:1 pages:12 https://doi.org/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a kostenfrei http://link.springer.com/article/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/toc/1478-811X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2018 1 12
allfieldsGer	10.1186/s12964-018-0256-8 doi (DE-627)DOAJ031413129 (DE-599)DOAJaf1884eb1e0a43b986d6bddbbd3ed46a DE-627 ger DE-627 rakwb eng QH573-671 E. Besray Unal verfasserin aut Systems level expression correlation of Ras GTPase regulators 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein. Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology Christina Kiel verfasserin aut Hannah Benisty verfasserin aut Andrew Campbell verfasserin aut Karen Pickering verfasserin aut Nils Blüthgen verfasserin aut Owen J. Sansom verfasserin aut Luis Serrano verfasserin aut In Cell Communication and Signaling BMC, 2004 16(2018), 1, Seite 12 (DE-627)37375275X (DE-600)2126315-2 1478811X nnns volume:16 year:2018 number:1 pages:12 https://doi.org/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a kostenfrei http://link.springer.com/article/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/toc/1478-811X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2018 1 12
allfieldsSound	10.1186/s12964-018-0256-8 doi (DE-627)DOAJ031413129 (DE-599)DOAJaf1884eb1e0a43b986d6bddbbd3ed46a DE-627 ger DE-627 rakwb eng QH573-671 E. Besray Unal verfasserin aut Systems level expression correlation of Ras GTPase regulators 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein. Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology Christina Kiel verfasserin aut Hannah Benisty verfasserin aut Andrew Campbell verfasserin aut Karen Pickering verfasserin aut Nils Blüthgen verfasserin aut Owen J. Sansom verfasserin aut Luis Serrano verfasserin aut In Cell Communication and Signaling BMC, 2004 16(2018), 1, Seite 12 (DE-627)37375275X (DE-600)2126315-2 1478811X nnns volume:16 year:2018 number:1 pages:12 https://doi.org/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a kostenfrei http://link.springer.com/article/10.1186/s12964-018-0256-8 kostenfrei https://doaj.org/toc/1478-811X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2018 1 12
language	English
source	In Cell Communication and Signaling 16(2018), 1, Seite 12 volume:16 year:2018 number:1 pages:12
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topic_facet	Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors Medicine R Cytology
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Besray Unal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Systems level expression correlation of Ras GTPase regulators</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. 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callnumber-first	Q - Science
author	E. Besray Unal
spellingShingle	E. Besray Unal misc QH573-671 misc Ras small GTPases misc Tissue expression misc Gene expression network misc GTPase activating proteins misc Guanine nucleotide exchange factors misc Medicine misc R misc Cytology Systems level expression correlation of Ras GTPase regulators
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topic_title	QH573-671 Systems level expression correlation of Ras GTPase regulators Ras small GTPases Tissue expression Gene expression network GTPase activating proteins Guanine nucleotide exchange factors
topic	misc QH573-671 misc Ras small GTPases misc Tissue expression misc Gene expression network misc GTPase activating proteins misc Guanine nucleotide exchange factors misc Medicine misc R misc Cytology
topic_unstemmed	misc QH573-671 misc Ras small GTPases misc Tissue expression misc Gene expression network misc GTPase activating proteins misc Guanine nucleotide exchange factors misc Medicine misc R misc Cytology
topic_browse	misc QH573-671 misc Ras small GTPases misc Tissue expression misc Gene expression network misc GTPase activating proteins misc Guanine nucleotide exchange factors misc Medicine misc R misc Cytology
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title	Systems level expression correlation of Ras GTPase regulators
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title_full	Systems level expression correlation of Ras GTPase regulators
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author_browse	E. Besray Unal Christina Kiel Hannah Benisty Andrew Campbell Karen Pickering Nils Blüthgen Owen J. Sansom Luis Serrano
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title_sort	systems level expression correlation of ras gtpase regulators
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title_auth	Systems level expression correlation of Ras GTPase regulators
abstract	Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
abstractGer	Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
abstract_unstemmed	Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
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title_short	Systems level expression correlation of Ras GTPase regulators
url	https://doi.org/10.1186/s12964-018-0256-8 https://doaj.org/article/af1884eb1e0a43b986d6bddbbd3ed46a http://link.springer.com/article/10.1186/s12964-018-0256-8 https://doaj.org/toc/1478-811X
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up_date	2024-07-03T20:28:12.639Z
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In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. 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Systems level expression correlation of Ras GTPase regulators

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