Regulatory mechanism of Ras in intracellular Signal Transduction

点击翻译按钮获取中文摘要

Regulatory mechanisms and the physiological role of the Ras-mediated signaling pathway in hematopoietic BaF3 cells were analyzed. Involvement of the Ras-guanine nucleotide exchange factor mSos in IL-3-induced Ras activation was examined by the use of a stable transfectant that conditionally expresses dominant-negative mSos. We found that the dominant-negative mSos mutant inhibited Ras-regulated kinases such as ERK2, suggesting an important role of mSos in IL-3 signal transduction. Furthermore, Ras-dependent activation of JNK1 in response to IL-3 stimulation was observed. We also analyzed the roles of small GTP-binding proteins, Cdc42, Rac, and Rho in signaltransduction leading to JNK1 activation in a transient expression system. In regard with the tyrosine kinase ACK,a target of Cdc42, enhanced tyrosine phosphorylation of this protein was detected following temperature shift-down, hyperosmotic shock, and EGF treatment.