FEBS Letters | |
Regulation of the MAP kinase cascade in PC12 cells: B‐Raf activates MEK‐1 (MAP kinase or ERK kinase) and is inhibited by cAMP | |
Peraldi, P.2  Calleja, V.2  Van Obberghen, E.2  Calothy, G.1  Frödin, M.2  Scimeca, J.-C.2  Barnier, J.V.1  Filloux, C.2  | |
[1] CNRS URA 1443, Institut Curie, Université Paris II, 91905 Orsay Cédex, France;INSERM U 145, Faculté de Médecine, 06107 Nice Cédex 2, France | |
关键词: cAMP; B-Raf; MAP kinase; MEK; p21ras; PC12 cell; MAP kinase; mitogen-activated protein kinase; MEK; MAP kinase or ERK kinase; CPT-cAMP; 8-(4-chlorophenylthio)-cyclic-AMP; NGF; nerve growth factor; MBP; myelin basic protein; PMA; phorbol 12-myristate 13-acetate; PKA; cAMP-dependent protein kinase; PKC; protein kinase C; | |
DOI : 10.1016/0014-5793(94)01376-C | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
In PC12 cells, cAMP stimulates the MAP kinase pathway by an unknown mechanism. Firstly, we examined the role of calcium ion mobilization and of protein kinase C in cAMP-stimulated MAP kinase activation. We show that cAMP stimulates p44mapk independently of these events. Secondly, we studied the role of B-Raf in this process. We observed that NGF, PMA and cAMP induce the phosphorylation of B-Raf as well as an upward shift in its electrophoretic mobility. We show that B-Raf is activated following NGF and PMA treatment of PC12 cells, and that it can phosphorylate and activate MEK-1. However, cAMP inhibits B-Raf autokinase activity as well as its ability to phosphorylate and activate MEK-1. This inhibition is likely to be due to a direct effect since we found that PKA phosphorylates B-Raf in vitro. Further, we show that B-Raf binds to p21ras, but more important, this binding to p21ras is virtually abolished with B-Raf from PC12 cells treated with CPT-cAMP. Hence, these data indicate that the PKA-mediated phosphorylation of B-Raf hampers its interaction with p21ras, which is responsible for the PKA-mediated decrease in B-Raf activity. Finally, our work suggests that in PC12 cells, cAMP stimulates MAP kinase through the activation of an unidentified MEK kinase and/or the inhibition of a MEK phosphatase.
【 授权许可】
Unknown
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