Genomic organization and regulation of the vav proto-oncogene

Diane J. Denkinger, Chad Borges, Connie L. Butler, Allison M. Cushman, Rodney S. Kawahara

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Vav and vav2 are members of the dbl family of guanine nucleotide exchange factors (GEF) for the rho/rac family of GTP binding proteins. Vav is expressed primarily in hematopoietic cells, while vav2 has a wider tissue distribution. The genomic structure of the human vav proto-oncogene was studied by identifying and sequencing all 27 exons of the gene from overlapping P1 and cosmid clones. The gene spans a 77-kb region on chromosome 19. In contrast, the coding region of vav2 is distributed over 30 exons spanning 227-kb. The overall organization of the exons which encode both proteins was found to be similar. In humans, alternative splicing of exons 6, 16 and 28 generated at least two distinct vav2 mRNA species. Several differences from the original vav cDNA sequence were noted. The most important difference was the identification of amino acid 718 as isoleucine, rather than threonine. This change warrants the reclassification of the vav SH2 domain as a type 3 SH2, instead of a type 2 SH2 as originally proposed by Songyang et al. (Mol. Cell. Biol. 14 (1994) 2777-2785). A series of vav promoter deletions were constructed using the enhanced green fluorescent protein (EGFP) as a reporter gene. A 23-bp segment that included a potential CBF/AML-1 binding site was found to be essential for EGFP expression in U937 cells. The same constructs were not active in HeLa cells, which do not express vav. A potential c-myb DNA binding site within the vav promoter was not required for EGFP expression. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1491
Issue number1-3
DOIs
StatePublished - Apr 25 2000
Externally publishedYes

Fingerprint

Proto-Oncogenes
Exons
Genes
rac GTP-Binding Proteins
Rho Guanine Nucleotide Exchange Factors
Binding Sites
Overlapping Genes
Chromosomes, Human, Pair 19
Cosmids
U937 Cells
src Homology Domains
Isoleucine
Alternative Splicing
Tissue Distribution
Threonine
Chromosomes
Reporter Genes
HeLa Cells
GTP-Binding Proteins
Complementary DNA

Keywords

  • EGFP
  • Hematopoietic
  • Regulation
  • Stem cells
  • Transcription
  • Vav

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

Cite this

Genomic organization and regulation of the vav proto-oncogene. / Denkinger, Diane J.; Borges, Chad; Butler, Connie L.; Cushman, Allison M.; Kawahara, Rodney S.

In: Biochimica et Biophysica Acta - Gene Structure and Expression, Vol. 1491, No. 1-3, 25.04.2000, p. 253-262.

Research output: Contribution to journalArticle

Denkinger, Diane J. ; Borges, Chad ; Butler, Connie L. ; Cushman, Allison M. ; Kawahara, Rodney S. / Genomic organization and regulation of the vav proto-oncogene. In: Biochimica et Biophysica Acta - Gene Structure and Expression. 2000 ; Vol. 1491, No. 1-3. pp. 253-262.
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