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The coordinated cross-talk from heterotrimeric G proteins to Rho GTPases is essential during a variety of physiological processes. Emerging data suggest that members of the Galpha(12/13) and Galpha(q/11) families of heterotrimeric G proteins signal downstream to RhoA via distinct pathways. Although studies have elucidated mechanisms governing Galpha(12/13)-mediated RhoA activation, proteins that functionally couple Galpha(q/11) to RhoA activation have remained elusive. Recently, the Dbl-family guanine nucleotide exchange factor (GEF) p63RhoGEF/GEFT has been described as a novel mediator of Galpha(q/11) signaling to RhoA based on its ability to synergize with Galpha(q/11) resulting in enhanced RhoA signaling in cells. We have used biochemical/biophysical approaches with purified protein components to better understand the mechanism by which activated Galpha(q) directly engages and stimulates p63RhoGEF. Basally, p63RhoGEF is autoinhibited by the Dbl homology (DH)-associated pleckstrin homology (PH) domain; activated Galpha(q) relieves this autoinhibition by interacting with a highly conserved C-terminal extension of the PH domain. This unique extension is conserved in the related Dbl-family members Trio and Kalirin and we show that the C-terminal Rho-specific DH-PH cassette of Trio is similarly activated by Galpha(q).

Titel:	Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain.
Autor/in / Beteiligte Person:	Rojas, RJ ; Yohe, ME ; Gershburg, S ; Kawano, T ; Kozasa, T ; Sondek, J
Link:	Full Text Finder (Volltext)
Zeitschrift:	The Journal of biological chemistry, Jg. 282 (2007-10-05), Heft 40, S. 29201-10
Veröffentlichung:	2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology ; <i>Original Publication</i>: Baltimore, MD : American Society for Biochemistry and Molecular Biology, 2007
Medientyp:	academicJournal
ISSN:	0021-9258 (print)
DOI:	10.1074/jbc.M703458200
Schlagwort:	Amino Acid Sequence Biochemistry methods Biophysics methods Dimerization GTP-Binding Protein alpha Subunits, Gq-G11 metabolism Guanine Nucleotide Exchange Factors chemistry Molecular Sequence Data Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Proto-Oncogene Proteins chemistry Rho Guanine Nucleotide Exchange Factors Sequence Homology, Amino Acid Signal Transduction GTP-Binding Protein alpha Subunits, Gq-G11 chemistry Guanine Nucleotide Exchange Factors metabolism Protein Serine-Threonine Kinases metabolism Proto-Oncogene Proteins metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Language: English [J Biol Chem] 2007 Oct 05; Vol. 282 (40), pp. 29201-10. <i>Date of Electronic Publication: </i>2007 Jul 02. MeSH Terms: GTP-Binding Protein alpha Subunits, Gq-G11 / chemistry ; Guanine Nucleotide Exchange Factors / metabolism ; Protein Serine-Threonine Kinases / metabolism ; Proto-Oncogene Proteins / metabolism ; Amino Acid Sequence ; Biochemistry / methods ; Biophysics / methods ; Dimerization ; GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism ; Guanine Nucleotide Exchange Factors / chemistry ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proto-Oncogene Proteins / chemistry ; Rho Guanine Nucleotide Exchange Factors ; Sequence Homology, Amino Acid ; Signal Transduction References: J Biol Chem. 2001 Nov 9;276(45):42527-33. 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(PMID: 11701921) Grant Information: P01 GM065533 United States GM NIGMS NIH HHS; P01-GM65533 United States GM NIGMS NIH HHS; R01 GM6145408 United States GM NIGMS NIH HHS; R01 GM062299-05A1 United States GM NIGMS NIH HHS; R01-GM62299 United States GM NIGMS NIH HHS; R01 GM062299 United States GM NIGMS NIH HHS Substance Nomenclature: 0 (ARHGEF25 protein, human) ; 0 (Guanine Nucleotide Exchange Factors) ; 0 (MCF2 protein, human) ; 0 (Proto-Oncogene Proteins) ; 0 (Rho Guanine Nucleotide Exchange Factors) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; EC 2.7.11.1 (TRIO protein, human) ; EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11) Entry Date(s): Date Created: 20070704 Date Completed: 20071107 Latest Revision: 20211203 Update Code: 20231215 PubMed Central ID: PMC2655113

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Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain.