ALPHA-SUBUNIT OF FARNESYLTRANSFERASE IS PHOSPHORYLATED IN-VIVO - EFFECT OF PROTEIN PHOSPHATASE-1 ON ENZYMATIC-ACTIVITY

Farnesyltransferase is a heterodimer consisting of a 49 kDa alpha-subu nit and a 46 kDa beta-subunit. In this report, we demonstrate that the endogenous heterodimeric farnesyltransferase protein is phosphorylate d at the alpha-subunit in vivo and phosphorylation plays a role in the regulation of farnesyltransferase activity. in vivo P-32-labeling of PC-12 cells followed by immunoprecipitation with specific anti rat alp ha-subunit IgG showed a labeled alpha-subunit protein band at an expec ted molecular mass of 49 kDa. Treatment of PC-12 cells with protein ph osphatase inhibitor, Calyculin A, resulted in a decrease in FTase acti vity, and phophoserine/phosphothreonine-specific protein phosphatase-1 treatment of PC-12 and GM37 cell extracts resulted in 100% and 375% i ncrease in farnesyltransferase activity, respectively, compared to unt reated extracts. (C) 1996 Academic Press, Inc.