THE PROONCOPROTEIN EWS BINDS CALMODULIN AND IS PHOSPHORYLATED BY PROTEIN-KINASE-C THROUGH AN IQ DOMAIN

A growing family of proteins is regulated by protein kinase C and calm odulin through IQ domains, a regulatory motif originally identified in neuromodulin (Alexander, K. A., Wakim, B. T., Doyle, G. S., Walsh, K. A., and Storm, D. R. (1988) J. Biol. Chem, 263, 7544-7549). Here we r eport that EWS, a nuclear RNA-binding proonco-protein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calm odulin, Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes wi th PKC phosphorylation, Several other RNA-binding proteins, including TLS/FUS and PSF, co-purify with EWS, PKC phosphorylation of these prot eins also inhibits their binding to RNA in vitro. These data suggest t hat PKC may regulate interactions of EWS and other RNA-binding protein s with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing.