FEBS Lett 1995,
PMID: 7835430
Peraldi, P; Frödin, M; Barnier, J V; Calleja, V; Scimeca, J C; Filloux, C; Calothy, G; Van Obberghen, E
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.
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Text Mining Data
MEK-1 → B-Raf: "
Regulation of the MAP kinase cascade in PC12 cells :
B-Raf activates
MEK-1 ( MAP kinase or ERK kinase ) and is inhibited by cAMP
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B-Raf → NGF: "
We observed that NGF , PMA and cAMP induce the phosphorylation of B-Raf as well as an upward shift in its electrophoretic mobility
"
B-Raf ⊣ PKA: "
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
"
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