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Identification of a JAK2-independent Pathway Regulating Growth Hormone (GH)-stimulated p44/42 Mitogen-activated Protein Kinase Activity

2002; Elsevier BV; Volume: 277; Issue: 47 Linguagem: Inglês

10.1074/jbc.m201385200

1083-351X

Tao Zhu, Ling Ling, Peter E. Lobie,

FOXO transcription factor regulation

We have demonstrated here that growth hormone (GH) stimulates the formation of the active GTP-bound form of both RalA and RalB in NIH-3T3 cells. Full activation of RalA and RalB by GH required the combined activity of c-Src and JAK2, both kinases activated by GH independent of the other. Activation of RalA and RalB by growth hormone did not require the activity of JAK2 per se . Ras was also activated by GH and was required for the GH-stimulated formation of GTP-bound RalA and RalB. Activation of RalA by GH subsequently resulted in increased phospholipase D activity and the formation of its metabolite, phosphatidic acid. GH-stimulated RalA-phospholipase D-dependent formation of phosphatidic acid was required for activation of p44/42 MAPK and subsequent Elk-1-mediated transcription stimulated by GH. Thus we report the identification of a JAK2-independent pathway regulating GH-stimulated p44/42 MAPK activity.