14] GTPase-activating protein activity of n(α1)-chimaerin and effect of lipids

Abstract

Publisher Summary This chapter describes the GTPase-activating protein (GAP) activity of n (α 1 )-chimerin and the effect of lipids. n (α 1 )-Chimerin cDNA encodes a 38-kDa GAP for Rac1 and Cdc42Hs, which possesses a protein kinase C (PKC)-like cysteine-rich regulatory domain. The cysteine-rich domain of n -chimerin coordinates 2 mol of Zn 2+ per mole protein and binds phorbol esters. Zn 2+ is required for n -chimerin and PKC to bind phorbol esters. n -Chimerin is a novel functional target for phorbol esters and phospholipids. Other proteins with a sequence identity to the cysteine-rich regulatory domain of n -chimerin are the oncogene products, Raf and Vav, diacylglycerol kinase, and the Caenorhabditis elegans unc-13 gene product. Similarly, a number of proteins have sequence a identity to the C-terminal GAP domain of n -chimerin, including Cdc42Hs–GAP, breakpoint cluster region gene product (Bcr), active Bcr-related gene product (Abr), and the Ras–GAP binding protein p190. The chimerin family of proteins consists of a cysteine-rich domain coupled to a GAP domain with variable N -terminal sequences.