| pubmed-article:11606575 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0242957 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0919267 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0027627 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0069515 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0033414 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C1419227 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:11606575 | lifeskim:mentions | umls-concept:C0813622 | lld:lifeskim |
| pubmed-article:11606575 | pubmed:issue | 52 | lld:pubmed |
| pubmed-article:11606575 | pubmed:dateCreated | 2001-12-25 | lld:pubmed |
| pubmed-article:11606575 | pubmed:abstractText | In this study we initially examined the interaction between CD44v3 (a hyaluronan (HA) receptor) and Vav2 (a guanine nucleotide exchange factor) in human ovarian tumor cells (SK-OV-3.ipl cell line). Immunological data indicate that both CD44v3 and Vav2 are expressed in SK-OV-3.ipl cells and that these two proteins are physically linked as a complex in vivo. By using recombinant fragments of Vav2 and in vitro binding assays, we have detected a specific binding interaction between the SH3-SH2-SH3 domain of Vav2 and the cytoplasmic domain of CD44. In addition, we have observed that the binding of HA to CD44v3 activates Vav2-mediated Rac1 signaling leading to ovarian tumor cell migration. Further analyses indicate that the adaptor molecule, growth factor receptor-bound protein 2 (Grb2) that is bound to p185(HER2) (an oncogene product), is also associated with the CD44v3-Vav2 complex. HA binding to SK-OV-3.ipl cells promotes recruitment of both Grb2 and p185(HER2) to the CD44v3-Vav2 complex leading to Ras activation and ovarian tumor cell growth. In order to determine the role of Grb2 in CD44v3 signaling, we have transfected SK-OV-3.ipl cells with Grb2 mutant cDNAs (e.g. Delta N-Grb2 that has a deletion in the amino-terminal SH3 domain or Delta C-Grb2 that has a deletion in the carboxyl-terminal SH3 domain). Our results clearly indicate that the SH3 domain deletion mutants of Grb2 (i.e. the Delta N-Grb2 (and to a lesser extent the Delta C-Grb2) mutant) not only block their association with p185(HER2) but also significantly impair their binding to the CD44v3-Vav2 complex and inhibit HA/CD44v3-induced ovarian tumor cell behaviors. Taken together, these findings strongly suggest that the interaction of CD44v3-Vav2 with Grb2-p185(HER2) plays an important role in the co-activation of both Rac1 and Ras signaling that is required for HA-mediated human ovarian tumor progression. | lld:pubmed |
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| pubmed-article:11606575 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:11606575 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:11606575 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11606575 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:11606575 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:HungM CMC | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:BourguignonL... | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:ZhuHH | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:ZhouBB | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:DiedrichFF | lld:pubmed |
| pubmed-article:11606575 | pubmed:author | pubmed-author:SingletonP... | lld:pubmed |
| pubmed-article:11606575 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11606575 | pubmed:day | 28 | lld:pubmed |
| pubmed-article:11606575 | pubmed:volume | 276 | lld:pubmed |
| pubmed-article:11606575 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11606575 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11606575 | pubmed:pagination | 48679-92 | lld:pubmed |
| pubmed-article:11606575 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:11606575 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11606575 | pubmed:articleTitle | Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth. | lld:pubmed |
| pubmed-article:11606575 | pubmed:affiliation | Enocrine Unit, Department of Medicine, University of California and Veterans Affairs Medical Center, San Francisco, California 94121, USA. lillyb@itsa.ucsf.edu | lld:pubmed |
| pubmed-article:11606575 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11606575 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:11606575 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:11606575 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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