Interleukin-7 activates p56lck and p59fyn, two tyrosine kinases associated with the p90 interleukin-7 receptor in primary human T cells.
We have investigated signaling events associated with the cloned 90-kDa (p90) interleukin-7 receptor (IL-7R) to determine whether changes in the signaling pathways initiated by this molecule can explain the ability of T cells to proliferate to IL-7 following activation. Using in vitro kinase assays we find that the p90 IL-7R in both unstimulated and activated human T cells is physically associated with two molecules with intrinsic kinase activity. Western blotting analysis reveals these proteins to be the src kinase enzymes, p59fyn and p56lck. Binding of human recombinant IL-7 to the p90 IL-7R results in increased activity of both receptor-associated kinases in both resting and activated mature T cells. Thus, the signaling pathways initiated via the p90 IL-7R-associated src kinases are unlikely to be solely responsible for the proliferation of only activated T cells in response to IL-7. Additional signals, which may derive from other IL-7R-associated molecules such as the gamma c, are clearly required for IL-7-driven proliferation of activated primary T cells.
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T H
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Kennedy Institute of Rheumatology, London, GB.
Lali
F V
FV
Foxwell
B M
BM
D015703:Antigens, CD / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D018123:Receptors, Interleukin / Q000378:metabolism*; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D019061:src-Family Kinases / Q000378:metabolism*
D015703:Antigens, CD; D015851:Interleukin-7; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases