[beta]3-Chimaerin, a novel member of the chimaerin Rac-GAP family

• Published in: Molecular biology reports Vol. 41; no. 4; p. 2067
• Main Authors: Zubeldia-brenner, Lautaro, Gutierrez-uzquiza, Alvaro, Barrio-real, Laura, Wang, Hongbin, Kazanietz, Marcelo G, Leskow, Federico Coluccio
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Nature B.V 01.04.2014
• Subjects: Molecular biology; Proteins; Signal transduction
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-014-3055-3

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 ([alpha]1- and [alpha]2-chimaerins) and CHN2 ([beta]1- and [beta]2-chimaerins) genes. Although these gene products are assumed to be generated by alternative splicing, bioinformatics analysis of the CHN2 gene revealed that [beta]1- and [beta]2-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 [beta]3-chimaerin. Expression profile analysis revealed predominantly low levels for the [beta]3-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, [beta]3-chimaerin has a unique N-terminal domain. Studies in cells established that [beta]3-chimaerin has Rac-GAP activity and is responsive to phorbol esters. The enhanced responsiveness of [beta]3-chimaerin for phorbol ester-induced translocation relative to [beta]2-chimaerin suggests differential ligand accessibility to the C1 domain. [PUBLICATION ABSTRACT]