Linked Life Data

21352810

Source:http://linkedlifedata.com/resource/pubmed/id/21352810

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-28
pubmed:abstractText
Invadopodia are cellular structures that are thought to mediate tumor invasion. ASAP1, an Arf GTPase-activating protein (GAP) containing a BAR domain, is a substrate of Src. ASAP1 is required for the assembly of invadopodia and podosomes, which are Src-induced structures related to invadopodia in NIH 3T3 fibroblasts. The BAR domain of ASAP1 is required for the assembly of podosomes. Using two-hybrid screening, we have identified GEFH1, a guanine nucleotide exchange factor for RhoA, as a binding partner of the BAR domain of ASAP1. We validated the interaction of endogenous GEFH1 with ASAP1 by immunoprecipitation, and found GEFH1 colocalized with ASAP1 in podosomes. The overexpression of GEFH1 inhibited podosome assembly and ASAP1 catalytic activity as a GAP. A mutant of GEFH1 lacking the domain that binds to the BAR domain of ASAP1 was less effective. Reduced expression of GEFH1, achieved with siRNA treatment, did not affect matrix degradation by podosomes but increased the rate of podosome assembly. Based on these results, we conclude that GEFH1 is a negative regulator of podosomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Published by Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
406
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
574-9
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
GEFH1 binds ASAP1 and regulates podosome formation.
pubmed:affiliation
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bldg 37 Room 2042, Bethesda, MD 20892, United States.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural