title: β3-chimaerin, a novel member of the chimaerin Rac-GAP family.
abstract: Chimaerins are a family of diacylglycerol- and phorbol ester-regulated GTPase activating proteins (GAPs) for the small G-protein Rac. Extensive evidence indicates that these proteins play important roles in development, axon guidance, metabolism, cell motility, and T cell activation. Four isoforms have been reported to-date, which are products of CHN1 (α1- and α2-chimaerins) and CHN2 (β1- and β2-chimaerins) genes. Although these gene products are assumed to be generated by alternative splicing, bioinformatics analysis of the CHN2 gene revealed that β1- and β2-chimaerins are the products of alternative transcription start sites (TSSs) in different promoter regions. Furthermore, we found an additional TSS in CHN2 gene that leads to a novel product, which we named β3-chimaerin. Expression profile analysis revealed predominantly low levels for the β3-chimaerin transcript, with higher expression levels in epididymis, plasma blood leucocytes, spleen, thymus, as well as various areas of the brain. In addition to the prototypical SH2, C1, and Rac-GAP domains, β3-chimaerin has a unique N-terminal domain. Studies in cells established that β3-chimaerin has Rac-GAP activity and is responsive to phorbol esters. The enhanced responsiveness of β3-chimaerin for phorbol ester-induced translocation relative to β2-chimaerin suggests differential ligand accessibility to the C1 domain.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina.
authors.forename: Lautaro
authors.initials: L
authors.lastname: Zubeldia-Brenner
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gutierrez-Uzquiza
authors.forename: Laura
authors.initials: L
authors.lastname: Barrio-Real
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wang
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Kazanietz
authors.forename: Federico Coluccio
authors.initials: FC
authors.lastname: Leskow
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D020740:Chimerin Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020740:Chimerin Proteins; D020033:Protein Isoforms; C000593185:chimaerin-beta3 protein, human; D020744:rac GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate