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rdf:type |
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lifeskim:mentions |
umls-concept:C0020792,
umls-concept:C0037083,
umls-concept:C0086376,
umls-concept:C0439855,
umls-concept:C0441655,
umls-concept:C0606872,
umls-concept:C0678594,
umls-concept:C1334043,
umls-concept:C1511545,
umls-concept:C1514562,
umls-concept:C1704735,
umls-concept:C1709915,
umls-concept:C1710082,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1948023,
umls-concept:C2003941,
umls-concept:C2697616
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pubmed:issue |
23
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pubmed:dateCreated |
2011-6-6
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pubmed:databankReference |
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pubmed:abstractText |
RH-RhoGEFs are a family of guanine nucleotide exchange factors that contain a regulator of G protein signaling homology (RH) domain. The heterotrimeric G protein G?(13) stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which G?(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in G?(13) that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of G?(13) to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by G?(13) and not through its interaction with a secondary binding site. A crystal structure of G?(13) bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a G?(13)-G?(i1) chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by G?(13).
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20625-36
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pubmed:meshHeading |
pubmed-meshheading:21507947-Allosteric Regulation,
pubmed-meshheading:21507947-Animals,
pubmed-meshheading:21507947-Crystallography, X-Ray,
pubmed-meshheading:21507947-Enzyme Activation,
pubmed-meshheading:21507947-GTP-Binding Protein alpha Subunits, G12-G13,
pubmed-meshheading:21507947-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:21507947-Mice,
pubmed-meshheading:21507947-Multienzyme Complexes,
pubmed-meshheading:21507947-Mutation,
pubmed-meshheading:21507947-Protein Structure, Quaternary,
pubmed-meshheading:21507947-Protein Structure, Tertiary,
pubmed-meshheading:21507947-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Identification of critical residues in G(alpha)13 for stimulation of p115RhoGEF activity and the structure of the G(alpha)13-p115RhoGEF regulator of G protein signaling homology (RH) domain complex.
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pubmed:affiliation |
Department of Pharmacology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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