IL-2 stimulation of T lymphocytes induces sequential activation of mitogen-activated protein kinases and phosphorylation of p56lck at serine-59.
p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. p56lck is known to associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a critical role in both T lymphocyte development and activation. p56lck also associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds to its receptor. Using primary cultures of Con A-activated normal splenic mouse T lymphocytes, we observed an IL-2-induced sequence of events involving p56lck. We saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase activity, which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated protein kinases, maximal activation of which was observed after 10 min. We also observed an IL-2-induced shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck), which reached a maximum at 15 min, the level of p60lck remaining constant for up to 4 h thereafter. This IL-2-induced shift correlated with the phosphorylation of serine-59 of p56lck, a site that mitogen-activated protein kinases are capable of modifying in vitro. The implications of these results for the understanding of both p56lck function and lymphoid cell receptor signaling pathways are discussed.
Watts
J D
JD
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Welham
M J
MJ
Kalt
L
L
Schrader
J W
JW
Aebersold
R
R
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D008970:Molecular Weight; D010449:Peptide Mapping; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
D007376:Interleukin-2; D012694:Serine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1