|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1996 : ¥1,600,000 (Direct Cost : ¥1,600,000)
IL-2 signal is transmitted by IL-2 receptor complex composed of alpha, beta and gamma chains. At least three signaling pathways have been demonstrated to be linked to the IL-2R ; the src-family PTK-linked c-fos/c-jun induction pathway, the c-myc induction pathway, and the bcl-2 induction pathway. All of these pathways are essential for IL-2 proliferative signaling, since these three pathways cooperate with each other to ensure a full range of signal transmission following IL-2 stimulation. Human T cell leukemia virus type I(HTLV-I)is the etiologic agent of adult T cell leukemia(ATL). Although p40tax-1, which is encoded by HTLV-1, activates transcription of viral and cellular genes, the mechanism(s)by which p40tax-1 promotes leukemogenesis in ATL is not fully understood. In the present study, we provide evidence that p40tax-1 can cooperate with the activated form (lck F505)of p56lck, or c-Myc but not with Bcl-2 to promote IL-2 or interleukin3(IL-3)-independent proliferation. Recently, we have shown that protein-tyrosine phosphatase SHP-2 is tyrosine phosphorylated by IL-2 stimulation. S-region and A-region of IL-2R beta is required for SHP-2 phosphorylation and src-family kinase, Lyn is important for this event.
The interleukin-2 receptor(IL-2R)is associated with the Jak1 and Jak3 PTKs, and ligand-induced activation of these PTKs is essential for lymphocyte proliferation. Recently, the non-receptor PTK,Pyk2, was found to be activated following IL-2 stimulation in a Jak-dependent manner. Furthermore, physical association was detected between endogenous Pyk2 and Jak3, and a dominant interfering mutant of Pyk2 inhibited IL-2-induced cell proliferation without affecting Stat5 activation. Collectively, these results suggest that Pyk2 is a newly identified component of the Jak-mediated IL-2 signalling pathway.