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|Title:||Src-CrkII-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities|
|Citation:||Ling, L., Zhu, T., Lobie, P.E. (2003-07-18). Src-CrkII-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities. Journal of Biological Chemistry 278 (29) : 27301-27311. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M302516200|
|Abstract:||We demonstrate here that growth hormone (GH) stimulates the activation of Rap1 and Rap2 in NIH-3T3 cells. Full activation of Rap1 and Rap2 by GH necessitated the combined activity of both JAK2 and c-Src kinases, although c-Src was predominantly required. GH-stimulated Rap1 and Rap2 activity was also demonstrated to be CrkII-C3G-dependent. GH stimulated the tyrosine phosphorylation of C3G, which again required the combined activity of JAK2 and c-Src. C3G tyrosine residue 504 was required for GH-stimulated Rap activation. Activated Rap1 inhibited GH-stimulated activation of RalA and subsequent GH-stimulated p44/42 MAP kinase activity and Elk-1-mediated transcription. In addition, we demonstrated that C3G-Rap1 mediated CrkII enhancement of GH-stimulated JNK/SAPK activity. We have therefore identified a linear JAK2-independent pathway switching GH-stimulated p44/42 MAP kinase and JNK/SAPK activities.|
|Source Title:||Journal of Biological Chemistry|
|Appears in Collections:||Staff Publications|
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