Interleukin-7 induces T cell proliferation in the absence of Erk/MAP kinase activity.
Interleukin (IL)-7 and IL-2 are important lymphoproliferative cytokines which both use the gamma c chain as part of their respective receptors. To learn more of their signaling mechanisms a comparison was made of the patterns of intracellular tyrosine phosphorylated proteins induced by these cytokines in the murine T cell line, CT6. Several similarities were revealed in the tyrosine phosphorylated proteins induced. However, a notable subset of proteins of mainly < 60 kDa were only phosphorylated by IL-2. Characterization of the two most prominent bands of this subset, pp54 and pp42, revealed these to contain Shc and p42MAP/Erk kinase, respectively. Further studies confirmed that IL-7 was unable to induce the phosphorylation of either the p44MAP/Erk or p42MAP/Erk or activation of the kinases. Shc is involved in activation of p21ras, a key event in the signaling cascade, via p72raf and MEK, leading to MAP/Erk kinase (MAPK) activation. These data indicate that this pathway is not utilized by IL-7 and may not, therefore, be essential for cytokine-driven T cell proliferation. This possibility was supported by studies with the MEK inhibitor PD098059, which had no selective effect on CT6 proliferation induced by IL-2 as compared with IL-7, although the drug completely inhibited MAP/Erk phosphorylation induced by IL-2.
Crawley
J B
JB
Mathilda & Terence Kennedy Institute of Rheumatology, Hammersmith, London, GB.
Willcocks
J
J
Foxwell
B M
BM
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D055504:Insulin Receptor Substrate Proteins; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D048369:MAP Kinase Kinase 1; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D055504:Insulin Receptor Substrate Proteins; D007376:Interleukin-2; D015851:Interleukin-7; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases