title: Alternative splicing variants of the human DBL (MCF-2) proto-oncogene.
abstract: The DBL (MCF-2) proto-oncogene is a prototype guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. In this communication we describe the isolation of three novel splicing variants of Dbl. The prototype Dbl gene (designated var.1 here) contains 25 exons, while splicing variant 2 (var.2) lacks exons 23 and 24. Var.3 contains additional 3 exons from 5(')-UTR in place of exon 1, while var.4, var.2, and var.3 contain a 48bp insertion between exons 10 and 11, resulting in the insertion of 16 amino acids. We found that var.1 was expressed only in brain, whereas var.3 was expressed in heart, kidney, spleen, liver, and testis, and var.4 in brain, heart, kidney, testis, placenta, stomach, and peripheral blood. The Dbl protein was detectable in brain, heart, kidney, intestine, muscle, lung, and testis. An assay for GEF activity revealed that the var.2 exhibits decreased GEF activity towards Cdc42, var.3 exhibits a weak but significant activity toward Rac1 and Cdc42, var.4 exhibits significant activity toward RhoA and Cdc42, while var.1 exhibits no activity toward RhoA, Rac1, or Cdc42. In summary, we describe 4 splicing variants of the human DBL proto-oncogene that show different tissue distributions and GEF specificities.
authors.affiliation: Department of Rheumatology, Kobe University, FHS School of Medicine, 7-10-2 Tomogaoka Suma, Kobe, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Komai
authors.forename: Rie
authors.initials: R
authors.lastname: Okayama
authors.forename: Michinori
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shiozawa
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D005091:Exons; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C000715470:MAS1 protein, human; C057811:MCF2 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein