β3-Chimaerin, a novel member of the chimaerin Rac-GAP family

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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 h...

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Detalles Bibliográficos
Autores principales:	Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G., Leskow, F.C.
Formato:	JOUR
Materias:	C1 domain Chimaerin CHN2 Phorbol esters Rac-GAP alpha1 chimaerin alpha2 chimaerin beta1 chimaerin beta2 chimaerin beta3 chimaerin chimerin guanosine triphosphatase activating protein isoprotein phorbol ester unclassified drug chimaerin-beta3 protein, human phorbol 13 acetate 12 myristate protein binding Rac protein alternative RNA splicing amino terminal sequence article bioinformatics CHN1 gene CHN2 gene controlled study enzyme activity enzyme analysis epididymis exon genetic analysis human human cell human tissue leukocyte nucleotide sequence promoter region protein analysis protein domain protein expression spleen thymus tissue distribution transcription initiation site amino acid sequence animal antibody specificity cell line chemistry Chlorocebus aethiops COS 1 cell line drug effects enzyme activation gene expression gene expression profiling gene expression regulation gene order genetics metabolism molecular genetics Alternative Splicing Amino Acid Sequence Animals Base Sequence Cell Line Cercopithecus aethiops Chimerin Proteins COS Cells Enzyme Activation Gene Expression Gene Expression Profiling Gene Expression Regulation Gene Order Humans Molecular Sequence Data Organ Specificity Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Isoforms rac GTP-Binding Proteins Tetradecanoylphorbol Acetate
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_03014851_v41_n4_p2067_ZubeldiaBrenner
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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Sumario:	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. © 2014 Springer Science+Business Media Dordrecht.

β3-Chimaerin, a novel member of the chimaerin Rac-GAP family

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