Regulation of SRC-family protein tyrosine kinases by interleukins, IL-2, and IL-3.
Unlike many other growth factor receptors, the known subunits of the receptors for the Interleukins IL-2 and IL-3 lack intrinsic tyrosine kinase activity, and yet increases in the phosphorylation of proteins on tyrosines is a rapid event in hematolymphoid cells following stimulation with these lymphokines. Here we show that IL-2 and IL-3 regulate the activity of specific members of the SRC-family of non-receptor protein tyrosine kinases (PTKs). In IL-2-dependent T-cell lines, IL-2 induced rapid and transient increases in the activity of the p56-LCK kinase without influencing the activities of other SRC-like PTKs (p59-FYN, p62-YES) in these T-lymphocytes. In contrast to IL-2's effects on p56-LCK in T-cells, studies of an IL-2-responsive cell line of the B-cell lineage that lacks p56-LCK revealed that IL-2 specifically regulates the activity of the p53/56-LYN kinase. Thus, some flexibility exists in the ability of various SRC-like PTKs to functionally couple to IL-2 signalling pathways. In several IL-3-dependent myeloid-committed leukemic cell lines, IL-3 was found to specifically regulate the activity of the p53/56-LYN kinase without affecting the activities of other SRC-like PTKs (p59/64-HCK, p59-FYN, p62-YES) in these hematopoietic cells. This finding that p53/56-LYN can be regulated by both IL-2 in B-lineage cells and IL-3 in myeloid-committed cells demonstrates that the same SRC-family PTK can participate in signal transduction events mediated via two independent receptor systems. Taken together, our findings imply that the specific combinations of lymphokine receptors and SRC-like PTKs available for coupling with those receptors are coordinately controlled during the differentiation of hematopoietic cells.
Torigoe
T
T
University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia.
O-Connor
R
R
Fagard
R
R
Fischer
S
S
Santoli
D
D
Reed
J C
JC
D000818:Animals; D002460:Cell Line; D016391:Genes, src; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology*; D051379:Mice; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology*
D007376:Interleukin-2; D007377:Interleukin-3; D011494:Protein Kinases