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-subunit and a 46 kDa beta-subunit. In this report, we demonstrate that the endogenous heterodimeric farnesyltransferase protein is phosphorylated at the alpha-subunit in vivo and phosphorylation plays a role in the regulation of farnesyltransferase activity. In vivo 32P-labeling of PC-12 cells followed by immunoprecipitation with specific anti rat alpha-subunit IgG showed a labeled alpha-subunit protein band at an expected molecular mass of 49 kDa. Treatment of PC-12 cells with protein phosphatase inhibitor, Calyculin A, resulted in a decrease in FTase activity, and phophoserine/phosphothreonine-specific protein phosphatase-1 treatment of PC-12 and GM37 cell extracts resulted in 100% and 375% increase in farnesyltransferase activity, respectively, compared to untreated extracts.
Kumar
A
A
Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock 72205, USA.
Beresini
M H
MH
Dhawan
P
P
Mehta
K D
KD
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase; D015151:Immunoblotting; D007074:Immunoglobulin G; D007700:Kinetics; D046911:Macromolecular Substances; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D016716:PC12 Cells; D010710:Phosphates / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D051381:Rats; D014166:Transferases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D008387:Marine Toxins; D010080:Oxazoles; D010710:Phosphates; C059041:calyculin A; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1