Major transcript variants of VAV3, a new member of the VAV family of guanine nucleotide exchange factors

VAV3 is a new member of the VAV oncogene family with a strong homology to V AV and VAV2. A conceptual translation of the cDNA indicates that VAV3 is be tween 40 and 77% identical to VAV and VAV2 at the amino acid level in all i dentified functional motifs. This homology suggests that VAV3 occupies a si milar position in signal transduction as the other family members. A major variant transcript, VAV3.1, found in both humans and mice, appears to encod e only the 3' SH3-SH2-SH3 region, which suggests that it may substitute for the full-length isoform in functions mediated by this domain, or compete w ith the full-length isoform in functions mediated by more N-terminal motifs , VAV3.1 either is a partly unspliced mRNA or originates from a different p romoter. VAV3 transcripts are found in cells of hematopoietic origin, where VAV is primarily expressed. However, unlike, VAV: the VAV3 and VAV3.1 tran scripts are also found at varying levels in a wide variety of other tissues and cell lines. TGF-beta and EGF reversibly down-regulate the abundance of the VAV3.1 transcript in HaCaT keratinocytes, representing the first obser vation of transcript regulation of a member of the VAV family by a growth f actor. (C) 2000 Elsevier Science B.V. All rights reserved.