Linked Life Data

16954208

Source:http://linkedlifedata.com/resource/pubmed/id/16954208

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2006-10-24
pubmed:abstractText
The Dbl homology nucleotide exchange factors (GEFs) activate Rho family cytosolic GTPases in a variety of physiological and pathophysiological events. These signaling molecules typically act downstream of tyrosine kinase receptors and often facilitate nucleotide exchange on more than one member of the Rho GTPase superfamily. Three unique GEFs, i.e. p115, PDZ-RhoGEF, and LARG, are activated by the G-protein coupled receptors via the Galpha(12/13), and exhibit very selective activation of RhoA, although the mechanism by which this is accomplished is not fully understood. Based on the recently solved crystal structure of the DH-PH tandem of PDZ-RhoGEF in complex with RhoA (Derewenda, U., Oleksy, A., Stevenson, A. S., Korczynska, J., Dauter, Z., Somlyo, A. P., Otlewski, J., Somlyo, A. V., and Derewenda, Z. S. (2004) Structure (Lond.) 12, 1955-1965), we conducted extensive mutational and functional studies of the molecular basis of the RhoA selectivity in PDZ-RhoGEF. We show that while Trp(58) of RhoA is intimately involved in the interaction with the DH domain, it is not a selectivity determinant, and its interaction with PDZ-RhoGEF is unfavorable. The key selectivity determinants are dominated by polar contacts involving residues unique to RhoA. We find that selectivity for RhoA versus Cdc42 is defined by a small number of interactions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32891-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16954208-Amino Acid Sequence, pubmed-meshheading:16954208-Crystallography, X-Ray, pubmed-meshheading:16954208-Enzyme Activation, pubmed-meshheading:16954208-Epitopes, pubmed-meshheading:16954208-Guanine Nucleotide Exchange Factors, pubmed-meshheading:16954208-Hydrogen Bonding, pubmed-meshheading:16954208-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:16954208-Kinetics, pubmed-meshheading:16954208-Models, Molecular, pubmed-meshheading:16954208-Molecular Sequence Data, pubmed-meshheading:16954208-Mutation, pubmed-meshheading:16954208-Protein Structure, Secondary, pubmed-meshheading:16954208-Protein Structure, Tertiary, pubmed-meshheading:16954208-Sensitivity and Specificity, pubmed-meshheading:16954208-Sequence Homology, Amino Acid, pubmed-meshheading:16954208-rhoA GTP-Binding Protein
pubmed:year
2006
pubmed:articleTitle
The molecular basis of RhoA specificity in the guanine nucleotide exchange factor PDZ-RhoGEF.
pubmed:affiliation
Institute of Biochemistry and Molecular Biology, University of Wroclaw, 50-137 Wroclaw, Poland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural