Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2005-9-19
pubmed:abstractText
Wrch-1 is a Rho family GTPase that shares strong sequence and functional similarity with Cdc42. Like Cdc42, Wrch-1 can promote anchorage-independent growth transformation. We determined that activated Wrch-1 also promoted anchorage-dependent growth transformation of NIH 3T3 fibroblasts. Wrch-1 contains a distinct carboxyl-terminal extension not found in Cdc42, suggesting potential differences in subcellular location and function. Consistent with this, we found that Wrch-1 associated extensively with plasma membrane and endosomes, rather than with cytosol and perinuclear membranes like Cdc42. Like Cdc42, Wrch-1 terminates in a CAAX tetrapeptide (where C is cysteine, A is aliphatic amino acid, and X is any amino acid) motif (CCFV), suggesting that Wrch-1 may be prenylated similarly to Cdc42. Most surprisingly, unlike Cdc42, Wrch-1 did not incorporate isoprenoid moieties, and Wrch-1 membrane localization was not altered by inhibitors of protein prenylation. Instead, we showed that Wrch-1 is modified by the fatty acid palmitate, and pharmacologic inhibition of protein palmitoylation caused mislocalization of Wrch-1. Most interestingly, mutation of the second cysteine of the CCFV motif (CCFV > CSFV), but not the first, abrogated both Wrch-1 membrane localization and transformation. These results suggest that Wrch-1 membrane association, subcellular localization, and biological activity are mediated by a novel membrane-targeting mechanism distinct from that of Cdc42 and other isoprenylated Rho family GTPases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33055-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16046391-Amino Acid Motifs, pubmed-meshheading:16046391-Amino Acid Sequence, pubmed-meshheading:16046391-Animals, pubmed-meshheading:16046391-Biotin, pubmed-meshheading:16046391-Blotting, Western, pubmed-meshheading:16046391-Cell Adhesion, pubmed-meshheading:16046391-Cell Membrane, pubmed-meshheading:16046391-Cell Proliferation, pubmed-meshheading:16046391-Cysteine, pubmed-meshheading:16046391-Cytosol, pubmed-meshheading:16046391-Endosomes, pubmed-meshheading:16046391-Esters, pubmed-meshheading:16046391-Green Fluorescent Proteins, pubmed-meshheading:16046391-Mice, pubmed-meshheading:16046391-Microscopy, Fluorescence, pubmed-meshheading:16046391-Molecular Sequence Data, pubmed-meshheading:16046391-Mutagenesis, Site-Directed, pubmed-meshheading:16046391-Mutation, pubmed-meshheading:16046391-NIH 3T3 Cells, pubmed-meshheading:16046391-Palmitic Acid, pubmed-meshheading:16046391-Protein Binding, pubmed-meshheading:16046391-Protein Structure, Tertiary, pubmed-meshheading:16046391-Recombinant Proteins, pubmed-meshheading:16046391-Sequence Homology, Amino Acid, pubmed-meshheading:16046391-Signal Transduction, pubmed-meshheading:16046391-Transfection, pubmed-meshheading:16046391-cdc42 GTP-Binding Protein, pubmed-meshheading:16046391-rho GTP-Binding Proteins
pubmed:year
2005
pubmed:articleTitle
Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif.
pubmed:affiliation
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, 27599-7512, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural