Scar/WAVE-1, a Wiskott–Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold

摘要: WAVE proteins are members of the Wiskott–Aldrich syndrome protein (WASP) family scaffolding that coordinate actin reorganization by coupling Rho-related small molecular weight GTPases to mobilization Arp2/3 complex. We identified WAVE-1 in a screen for rat brain A kinase-anchoring (AKAPs), which bind SH3 domain Abelson tyrosine kinase (Abl). Recombinant interacts with cAMP-dependent (PKA) and Abl kinases when expressed HEK-293 cells, both enzymes co-purify endogenous from extracts. Mapping studies have defined binding sites each kinase. Competition experiments suggest PKA–WAVE-1 interaction may be regulated as binds site overlapping verprolin homology region, has been shown interact actin. Immunocytochemical analyses Swiss 3T3 fibroblasts scaffold is assembled dynamically WAVE, PKA translocate response platelet-derived growth factor treatment. Thus, we propose previously unrecognized function an actin-associated recruits Abl.