Lymphocyte activation provokes modification of a lymphocyte-specific protein tyrosine kinase (p56lck).
The protein tyrosine kinase p56lck is implicated in the control of lymphocyte growth by virtue of its overexpression in some lymphoid malignancies and its transforming activity in heterologous systems. Previous studies have demonstrated that levels of lck mRNA and of p56lck decline rapidly after T cell activation. The disappearance of p56lck results primarily from post-translational conversion of p56lck to more slowly migrating forms with apparent sizes of approximately 60 kDa. This modification can be provoked by treatment of lymphocytes with PMA, and has been associated with increased serine phosphorylation of the p56lck molecule. Here we demonstrate that conversion of p56lck to p60lck is a feature of the physiologic activation of T lymphocytes by antigen-presenting cells. In addition, we show that the PMA-induced modification of p56lck proceeds via a mechanism distinct from conventional protein kinase C activation. The rapid conversion of p56lck to p60lck after antigenic stimulation is consistent with the view that this membrane-associated protein tyrosine kinase regulates some aspects of the lymphocyte activation sequence.
Marth
J D
JD
Howard Hughes Medical Institute, Department of Biochemistry, Seattle, WA 98195.
Lewis
D B
DB
Cooke
M P
MP
Mellins
E D
ED
Gearn
M E
ME
Samelson
L E
LE
Wilson
C B
CB
Miller
A D
AD
Perlmutter
R M
RM
D000328:Adult; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D005785:Gene Conversion / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008970:Molecular Weight; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D003208:Concanavalin A; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate