Stimulation of receptor protein-tyrosine phosphatase alpha activity and phosphorylation by phorbol ester

Abstrad Receptor Protein-Tyrosine Phosphatase a (RPTPa) is a transmembrane protein with two cytoplasmic catalytic protein-tyrosine phosphatase (PTP) domains and a relatively short (1 23 amino acids) extracellular domain. Here we report that treatment of transfeded cells that express RPTPa with the phorbol ester 12-0tetradecanoyl-phorbol-1 3-acetate, a dired adivator of protein kinase C, induced a rapid, transient increase in RPTPa adivity due to a 2to 3-fold increase in substrate affinity. A transient increase in RPTPa serine phosphorylation was concomitant with the enhanced activity. Tryptic phosphopeptide mapping of RPTPa demonstrated that phosphorylation of three tryptic peptides was enhanced in response to phorbol ester. In vitro dephosphorylation of RPTPa from phorbol estertreated cells reduced RPTPa adivity to prestimulation levels, indicating that enhanced serine phosphorylation diredly accounted for the increase in adivity. Our results demonstrate that serine phosphorylation may play a key role in the regulation of the adivity of transmembrane PTPs.