|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥1,700,000 (Direct Cost : ¥1,700,000)
The possible cross-talk between the signaling pathways from the receptors for erythropoietin (Epo) and interleukin-3(IL3) was first investigated. Epo stimulation was found to induce tyrosine phosphorylation of the beta chain of IL3 receptor and its binding with Stat5. Moreover, a Stat5 mutant, in which Y-694 required for activation of Stat5 was substituted, formed a stable complex with the IL3 receptor and inhibited its ability to activate Stat5 (Chin H.et al, Blood 89 : 4327-4336, 1997). Epo as well as IL3 also induced tyrosine phosphorylation of CrkL and its association with tyrosine phosphorylated signaling molecules including Shc, Syp, Cbl, and the Epo receptor (Chin H.et al, BBC 239 : 412-417, 1997). Lyn, a Src family tyrosine kinase, was found to bind the Epo receptor in vivo through the SH2 domain and to induce tyrosine phosphorylation of Stat5 as well as the Epo receptor and to activate the DNA binding and transactivating abilities of Stat5 ( Chin H.et al, Blood 91 : 3734-3745, 1998). We further investigated the function of CrkL in hematopoietic cells and found that CrkL activates integrins through C3G and thereby enhances cell adhesion (Arai A.et al, Blood, in press). CrkL was also found to mediate the activation of the Ras/Erk signaling pathway from the receptors for Epo and IL-3 through C3G (Nosaka Y.et al, submitted for publication).