title: Identification of a novel mouse Dbl proto-oncogene splice variant: evidence that SEC14 domain is involved in GEF activity regulation.
abstract: The Rho guanine nucleotide exchange factor protoDbl is involved in different biochemical pathways affecting cell proliferation and migration. The N-terminal sequence of protoDbl contains negative regulatory elements that restrict the catalytic activity of the DH-PH module. Here, we report the identification of a new mouse protoDbl splice variant lacking exon 3. We found that the splice variant mRNA is expressed in the spleen and bone marrow lymphocytes, adrenal gland, gonads and brain. The protoDbl variant protein was detectable in the brain. The newly identified variant displays the disruption of the SEC14 domain, positioned on exons 2 and 3 in the protoDbl N-terminal region. We show here that an altered SEC14 sequence leads to enhanced Dbl translocation to the plasma membrane and to augmented transforming and exchange activity.
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Ognibene
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vanni
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Blengio
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Segalerba
authors.affiliation: Department of Experimental Medicine, Università di Roma "La Sapienza", 00161 Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancini
authors.affiliation: Laboratory of Neurosurgery, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Marco
authors.affiliation: Department of Experimental Medicine, Università di Roma "La Sapienza", 00161 Roma, Italy; S. Andrea Hospital, 00161 Roma, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Torrisi
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bosco
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, 16147 Genova, Italy. Electronic address: alessandraeva@ospedale-gaslini.ge.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Eva
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D005091:Exons; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: C581598:Cdc42 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C000715470:MAS1 protein, human; C057811:MCF2 protein, human; C512843:Mcf2 protein, mouse; D049294:Phospholipid Transfer Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C483438:SEC14 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020764:cdc42 GTP-Binding Protein
keywords: 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride; AEBSF; Alternative splicing; CRAL; Cellular Retinaldehyde domain; DH; Dbl; Dbl homology; Diffuse Large B cell Lymphoma; GAPDH; GEF; Glyceraldehyde 3-phosphate dehydrogenase; Guanine nucleotide exchange factor; PAK-CRIB; PH; Pleckstrin homology; Rho GTPases; SEC14 protein domain; SEC14p; Saccaromyces cerevisiae phosphatidylinositol transfer protein domain; TRIO; Transforming activity; Triple functional domain; p21-Activated Kinase-Cdc42/Rac Interactive Binding; protoDbl oncogene