Treatment of T lymphocytes with a tumor-promoting phorbol ester causes the apparent down-regulation of a protein-tyrosine kinase

T lymphocytes possess a membrane-associated protein-tyrosine kinase of 56,000 Da (p56) that catalyzes an autophosphorylation reaction that leads to its modification on a tyrosine residue. The extent of p56 autophosphorylation is reduced in particulate fractions from cells that have been activated in vitro with the polyclonal mitogen concanavalin A. The percentage of the total acid-stable phosphoamino acids formed by in vitro phosphorylation decreases from 13 to 5 following mitogen activation. This decrease in autophosphorylating activity can be mimicked by incubating T cells for short periods of time with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA is a potent comitogen with phytohemagglutinin for the activation of T cells in culture. Labeling studies with (/sup 3/H) myristic acid indicate that the concentration of (/sup 3/H) myristoylated p56 is also decreased in membranes from TPA-treated cells. Treatment of cells that are prelabeled with (/sup 32/P)orthophosphate with TPA leads to the increased phosphorylation of p56 on serine residues, which is consistent with a role for protein kinase C in mediating the effects of TPA.