Source:http://linkedlifedata.com/resource/pubmed/id/17237826
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
28
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pubmed:dateCreated |
2007-6-14
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pubmed:abstractText |
The multi-functional protein c-Cbl is an important modulator of actin cytoskeletal dynamics in diverse biological systems. We had previously reported that c-Cbl facilitates cell spreading and adhesion and suppresses anchorage-independent growth of v-Abl-transformed fibroblasts. To assess the importance of membrane localization of c-Cbl for the observed effects of c-Cbl in v-Abl-3T3 cells, we first mapped the membrane interactive domain(s) of c-Cbl. Our studies indicate that localization of c-Cbl to the membrane is likely to be mediated by the tyrosine kinase binding (TKB) domain and the proline-rich region of c-Cbl, whereas C-terminal tyrosine phosphorylation does not play a role. The association of v-Cbl, which encompasses the TKB domain, with the membrane was unusual as it was not entirely dependent on SH2-phosphotyrosine interactions. Our studies further demonstrate that Src-like adaptor protein (SLAP), which binds to v-Cbl in a tyrosine phosphorylation-independent manner, facilitates membrane association of Cbl. The interaction between c-Cbl and SLAP in v-Abl-3T3 cells positively influenced c-Cbl-mediated spreading and adhesion of these cells. SLAP appears to exert its effects not simply by increasing the amount of c-Cbl in the membrane but by facilitating binding of p85-phosphatidylinositol-3-kinase (PI3K) with membrane-associated c-Cbl.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4095-105
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17237826-3T3 Cells,
pubmed-meshheading:17237826-Animals,
pubmed-meshheading:17237826-COS Cells,
pubmed-meshheading:17237826-Cell Transformation, Neoplastic,
pubmed-meshheading:17237826-Cercopithecus aethiops,
pubmed-meshheading:17237826-Fibroblasts,
pubmed-meshheading:17237826-Humans,
pubmed-meshheading:17237826-Jurkat Cells,
pubmed-meshheading:17237826-Mice,
pubmed-meshheading:17237826-Oncogene Proteins v-abl,
pubmed-meshheading:17237826-Phosphorylation,
pubmed-meshheading:17237826-Proto-Oncogene Proteins c-cbl
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pubmed:year |
2007
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pubmed:articleTitle |
c-Cbl-facilitated cytoskeletal effects in v-Abl-transformed fibroblasts are regulated by membrane association of c-Cbl.
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pubmed:affiliation |
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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