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

Autor: HongBin Wang, Marcelo G. Kazanietz, Laura Barrio-Real, Alvaro Gutierrez-Uzquiza, Federico Coluccio Leskow, Lautaro Zubeldia-Brenner
Rok vydání: 2014
Předmět:
Gene isoform
GTPase-activating protein
Otras Ciencias Biológicas
Molecular Sequence Data
Gene Expression
Chimaerin
Biology
Article
Cell Line
Ciencias Biológicas
chemistry.chemical_compound
Chlorocebus aethiops
Gene Order
Gene expression
Tyrosine Kinase Receptor
Genetics
Animals
Humans
Protein Isoforms
Protein Interaction Domains and Motifs
Amino Acid Sequence
Promoter Regions
Genetic
Molecular Biology
C1 domain
Regulation of gene expression
Base Sequence
Gene Expression Profiling
Alternative splicing
Chimerin Proteins
GAP
General Medicine
Molecular biology
Rac
rac GTP-Binding Proteins
Enzyme Activation
Rac GTP-Binding Proteins
Alternative Splicing
Gene Expression Regulation
chemistry
Organ Specificity
COS Cells
Phorbol
Tetradecanoylphorbol Acetate
CIENCIAS NATURALES Y EXACTAS
Protein Binding
Zdroj: Molecular Biology Reports. 41:2067-2076
ISSN: 1573-4978
0301-4851
DOI: 10.1007/s11033-014-3055-3
Popis: 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. Fil: Zubeldia Brenner, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gutierrez Uzquiza, Alvaro. University of Pennsylvania; Estados Unidos Fil: Barrio Real, Laura. University of Pennsylvania; Estados Unidos Fil: Wang, Hongbin. University of Pennsylvania; Estados Unidos Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos Fil: Coluccio Leskow, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina
Databáze: OpenAIRE
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