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.
Documento: | Artículo |
Título: | β3-Chimaerin, a novel member of the chimaerin Rac-GAP family |
Autor: | Zubeldia-Brenner, L.; Gutierrez-Uzquiza, A.; Barrio-Real, L.; Wang, H.; Kazanietz, M.G.; Leskow, F.C. |
Filiación: | Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104-6160, United States Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, 6700, Argentina |
Idioma: | Inglés |
Palabras clave: | C1 domain; Chimaerin; CHN2; Phorbol esters; Rac-GAP |
Año: | 2014 |
Página de inicio: | 1 |
Página de fin: | 10 |
DOI: | http://dx.doi.org/10.1007/s11033-014-3055-3 |
Título revista: | Molecular Biology Reports |
Título revista abreviado: | Mol. Biol. Rep. |
ISSN: | 03014851 |
CODEN: | MLBRB |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03014851_v_n_p1_ZubeldiaBrenner |