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The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA

The monomeric GTPase RhoA, which is a key regulator of numerous cellular processes, is activated by a variety of G protein-coupled receptors, through either G12 or G(q) family proteins. Here we report that p63RhoGEF, a recently identified RhoA-specific guanine nucleotide exchange factor, enhances th...

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Main Authors: Lutz, Susanne (Author) , Freichel-Blomquist, Andrea (Author) , Yang, Yang (Author) , Rümenapp, Ulrich (Author) , Jakobs, Karl-Heinz (Author) , Schmidt, Martina (Author) , Wieland, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 4 January 2005
In: The journal of biological chemistry
Year: 2005, Volume: 280, Issue: 12, Pages: 11134-11139
ISSN:1083-351X
DOI:10.1074/jbc.M411322200
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M411322200
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Author Notes:Susanne Lutz, Andrea Freichel-Blomquist, Yang Yang, Ulrich Rümenapp, Karl H. Jakobs, Martina Schmidt, Thomas Wieland
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Summary:The monomeric GTPase RhoA, which is a key regulator of numerous cellular processes, is activated by a variety of G protein-coupled receptors, through either G12 or G(q) family proteins. Here we report that p63RhoGEF, a recently identified RhoA-specific guanine nucleotide exchange factor, enhances the Rho-dependent gene transcription induced by agonist-stimulated G(q/11)-coupled receptors (M3-cholinoceptor, histamine H1 receptor) or GTPase-deficient mutants of G alpha(q) and G alpha11. We further demonstrate that active G alpha(q) or G alpha11, but not G alpha12 or G alpha13, strongly enhances p63RhoGEF-induced RhoA activation by direct protein-protein interaction with p63RhoGEF at its C-terminal half. Moreover, the activation of p63RhoGEF by G alpha(q/11) occurs independently of and in competition to the activation of the canonical G alpha(q/11) effector phospholipase C beta. Therefore, our results elucidate a new signaling pathway by which G alpha(q/11)-coupled receptors specifically induce Rho signaling through a direct interaction of activated G alpha(q/11) subunits with p63RhoGEF.
Item Description:Im Titel ist "q/11" in Gq/11 tiefgestellt
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Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M411322200

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