Schramm K, Niehof M, Radziwill G, Rommel C, Moelling K
Max-Planck-Institut fuer Molekulare Genetik, Abt. Schuster, Berlin (Dahlem), FRG.
Biochem Biophys Res Commun. 1994 Jun 15;201(2):740-7. doi: 10.1006/bbrc.1994.1763.
c-Raf-1 is a serine/threonine-specific protein kinase which is regulated by phosphorylation. A putative c-AMP dependent protein kinase PKA phosphorylation site with the consensus sequence RRXS, Ser43, and a predominant phosphorylation site of c-Raf-1, Ser259, can be phosphorylated by PKA in vitro as shown by comparison of phosphopeptide maps of recombinant wild-type c-Raf-1 and the corresponding mutants. In vivo stimulation of the PKA pathway by treatment of A431 cells with Forskolin results in increase of phosphorylation in Ser43. Forskolin reduces the upshift of c-Raf-1 induced by EGF-treatment. It inhibits the EGF-activation of the c-Raf-1 protein kinase activity tested in vitro with a peptide substrate.
c-Raf-1是一种丝氨酸/苏氨酸特异性蛋白激酶，受磷酸化作用调控。一个具有RRXS共有序列的假定c-AMP依赖性蛋白激酶PKA磷酸化位点（Ser43）以及c-Raf-1的主要磷酸化位点Ser259，如重组野生型c-Raf-1和相应突变体的磷酸肽图谱比较所示，在体外可被PKA磷酸化。用福斯高林处理A431细胞在体内刺激PKA途径会导致Ser43磷酸化增加。福斯高林减少了表皮生长因子（EGF）处理诱导的c-Raf-1的上移。它抑制了用肽底物在体外测试的c-Raf-1蛋白激酶活性的EGF激活。
