Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1

Abstract

A novel widely expressed homologue of the VAV oncogene, VAV2 (53% identical residues), has been identified within the critical region for the tuberous sclerosis gene, TSC1, on human chromosome 9q34. By Southern blot analysis, analysis of allele-specific transcription, and direct sequencing of the VAV2 mRNA/cDNA from patient lymphoblastoid cell lines, we demonstrate that both alleles of this gene are expressed in TSC patients and there are no significant mutations. VAV consists of a novel array of signalling domains and is thought to play an important role in signal transduction in haematopoietic tissues where it is exclusively expressed. VAV2 is likely to serve a similar role more generally in mammalian cells, but is not the TSC1 gene.

c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells via activation of small GTPases

“…Our results argue that similar roles may be played by Vav2 and CrkL, as well. Tyrosine phosphorylation of Vav2, a ubiquitously expressed form of Vav (Henske et al, 1995), known to activate Rho-like GTPases in a tyrosine phosphorylationdependent manner (Schuebel et al, 1998), is increased in both wild-type c-Cbl-and Tyr 5 -4Phe-overexpressing v-Abl-transformed NIH3T3 cells, as compared to vector control cells (data not shown). However, only wild-type c-Cbl is co-immunoprecipitated with Vav2 (data not shown), consistent with the previously shown role of tyrosine-700 of c-Cbl as the Vav-binding site for this protein (Marengere et al, 1997).…”

“…The analysis of morphology of transfected cells showed that expression of dominant-inhibitory p85 reduced their spreading on FN, while expression of wild-type p85 facilitated their spreading on FN as compared to the corresponding vector-transfected cells (Figure 8b). The Considering the importance of Vav GEFs for the activation of Rho-like GTPases, we also analysed tyrosine phosphorylation of Vav2, a ubiquitously expressed form of Vav (Henske et al, 1995), in control, c-Cbl-and Tyr 5 -4Phe-overexpressing v-Abl-transformed NIH3T3 cells. Tyrosine phosphorylation of Vav2 was increased both in cells expressing wild-type cCbl and in those expressing Tyr 5 -4Phe, as compared to vector control cells (data not shown).…”

Mutagenic analysis of Vav reveals that an intact SH3 domain is required for transformation

“…Sequence alignment of vavSH3C with other SH3 domains revealed that it is almost identical (98%) to the SH3 domain of vav2, another member of the vav family of proteins (Henske et al, 1995). As there is yet no structural or functional information relating to the SH3 domain of vav2, we searched for additional SH3 domains that resemble that of Vav.…”

Clinical Significance of Increased Guanine Nucleotide Exchange Factor Vav3 Expression in Human Gastric Cancer

“…The 3 mammalian Vav proteins (Vav1, Vav2, and Vav3) differ in their tissue distribution. Vav1 is primarily expressed in hematopoietic cells, whereas Vav2 and Vav3 are more ubiquitously expressed (12)(13)(14). Vav proteins contain multiple function motifs and are involved in various cellular signaling processes, including cytoskeleton organization, cell transformation, and oncogenesis (15,16).…”