IL-7 receptor mediates tyrosine phosphorylation but does not activate the phosphatidylinositol-phospholipase C-gamma 1 pathway.
IL-7 is a glycoprotein involved in the regulation of lymphocyte precursor growth. In addition, it has a comitogenic effect on mature T cells but not on mature B cells. The exact mechanism whereby IL-7R mediates these cell growth properties remains unknown. Because many growth factor receptor systems on various cell types transduce signals by activating a tyrosine kinase, we have studied here the effect of IL-7R ligation on protein tyrosine phosphorylation. We found that human rIL-7 consistently induced tyrosine phosphorylation of five major proteins, of 175, 155, 135, 110, and 85 kDa, and five minor proteins. The effect of human rIL-7 on tyrosine phosphorylation of these substrates was concentration and time dependent. One of the known substrates that is phosphorylated on tyrosine residues after binding of growth factors to their receptors is the phosphoinositide-specific phospholipase C. Several phospholipase C isozymes have been recently recognized; one isozyme, phospholipase C-gamma 1, was demonstrated to be phosphorylated rapidly after ligand binding to the platelet-derived growth factor receptor and the T cell Ag receptor. We show here that, in contrast to Ag receptor ligation, activation of IL-7R does not induce tyrosine phosphorylation on phospholipase C-gamma 1. Consistent with these results, human rIL-7 failed to increase phosphatidylinositol turnover and did not induce a rise in cytosolic free Ca2+ in the thymocytes, mature T cells, or pre-pre-B cells. The results indicate that the IL-7R mediates the activation of the tyrosine phosphorylation pathway but does not induce the phosphatidylinositol-phospholipase C pathway.
Roifman
C M
CM
Division of Immunology/Allergy, Hospital for Sick Children, Toronto, Ontario, Canada.
Wang
G X
GX
Freedman
M
M
Pan
Z Q
ZQ
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015851:Interleukin-7; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D014443:Tyrosine; D010738:Type C Phospholipases; D002118:Calcium