Linked Life Data

9057091

Source:http://linkedlifedata.com/resource/pubmed/id/9057091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-5-5
pubmed:abstractText
v-Crk is an oncogene product in which a viral Gag sequence is fused to a cellular Crk sequence. It contains one SH2 and one SH3 domain. To gain insight into the molecular mechanisms underlying v-Crk-induced cell transformation, we studied the subcellular localization and molecular interactions of v-Crk in v-Crk-transformed NIH-3T3 cells. Our results show that v-Crk specifically localizes to focal adhesions where it induces protein tyrosine phosphorylation. Subcellular fractionation studies indicated that a significant amount of v-Crk is present in the cytoskeletal cell fraction, a fraction that includes focal adhesions. Tyrosine phosphorylated proteins, including p130CAS, were also predominantly found in the cytoskeletal fraction. We show that v-Crk induces a translocation of p130CAS to the cytoskeleton, which is accompanied by hyperphosphorylation of this protein. Mutational analyses showed that functional v-Crk SH2 domain is required for the localization of v-Crk in focal adhesions. Functional v-Crk SH2 and SH3 domains were both found to be required for the observed increase in tyrosine phosphorylation of focal adhesion proteins and for the translocation and hyperphosphorylation of p130CAS. v-Crk immunoprecipitation studies revealed that cytoskeleton-associated v-Crk interacts with both p130CAS and an unidentified tyrosine kinase. These findings suggest that formation of a focal adhesion-located complex consisting of v-Crk, a tyrosine kinase and p130CAS, which may lead to the hyperphosphorylation of p130CAS. These specific and localized signaling events may represent initial steps in the process of v-Crk-induced cell transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
110 ( Pt 3)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
389-99
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9057091-3T3 Cells, pubmed-meshheading:9057091-Animals, pubmed-meshheading:9057091-Cell Adhesion, pubmed-meshheading:9057091-Cell Adhesion Molecules, pubmed-meshheading:9057091-Cell Line, Transformed, pubmed-meshheading:9057091-Cell Transformation, Neoplastic, pubmed-meshheading:9057091-Cell Transformation, Viral, pubmed-meshheading:9057091-Crk-Associated Substrate Protein, pubmed-meshheading:9057091-Cytoskeleton, pubmed-meshheading:9057091-Mice, pubmed-meshheading:9057091-Oncogene Protein v-crk, pubmed-meshheading:9057091-Phosphoproteins, pubmed-meshheading:9057091-Phosphorylation, pubmed-meshheading:9057091-Phosphotyrosine, pubmed-meshheading:9057091-Protein-Tyrosine Kinases, pubmed-meshheading:9057091-Proteins, pubmed-meshheading:9057091-Retinoblastoma-Like Protein p130, pubmed-meshheading:9057091-Retroviridae Proteins, Oncogenic, pubmed-meshheading:9057091-Signal Transduction, pubmed-meshheading:9057091-src Homology Domains
pubmed:year
1997
pubmed:articleTitle
v-Crk-induced cell transformation: changes in focal adhesion composition and signaling.
pubmed:affiliation
Department of Molecular Cell Biology, Institute of Biomembranes, Utrecht University, The Netherlands. mirjam@emsaserv.biol.ruu.nl
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't