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Interleukin‐2 signal transduction in human NK cells: multisite phosphorylation and activation of the tyrosine kinase p56 /ck
Author(s) -
Einspahr Kregg J.,
Abraham Robert T.,
Dick Christopher J.,
Leibson Paul J.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.5.565
Subject(s) - phosphorylation , tyrosine phosphorylation , biology , microbiology and biotechnology , tyrosine , kinase , receptor tyrosine kinase , tyrosine kinase , signal transduction , phosphorylation cascade , sh2 domain , protein phosphorylation , serine , biochemistry , protein kinase a
Interleukin‐2 (IL‐2) potently stimulates natural killer (NK) cell proliferation and cytotoxic function. However, the molecular mechanisms by which IL‐2 delivers activation signals from the IL‐2 receptor to the NK cell interior are incompletely understood. Previous studies demonstrated that IL‐2 stimulation induced the tyrosine phosphorylation of multiple proteins in NK cells, together with a prominent reduction in the elec‐ trophoretic mobility of p56 lac . The present studies indicate that IL‐2 induces a rapid (≤1 min) increase in the catalytic activity of p 56 lck , as measured by increases in protein tyrosine kinase activity in vitro. Furthermore, in response to IL‐2, p 56 lck itself undergoes complex alterations in serine and tyrosine phosphorylation. Cyanogen bromide cleavage maps indicate that IL‐2 stimulates a pronounced increase in the phosphorvlation of the NH2‐terminal region of p56 lck containing multiple known sites of serine phosphorylation. In addition, IL‐2 induced a marked increase in the phosphorylation of a COOH‐terminal peptide containing the regulatory Tyr‐505 residue of p56 lck . These results suggest that p56 lck serves as a substrate for both protein serine and tyrosine kinases activated during stimulation of this cell type with IL‐2. Furthermore, these results indicate that the pleiotropic effects of IL‐2 on NK cell physiology are initiated and regulated by a complex and multitiered interaction of different protein kinases including p56 lck .