Mark M D, Liu Y, Wong S T, Hinds T R, Storm D R
Department of Pharmacology, University of Washington, Seattle 98195, USA.
J Cell Biol. 1995 Aug;130(3):701-10. doi: 10.1083/jcb.130.3.701.
MAP kinase activity is necessary for growth factor induction of neurite outgrowth in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does not stimulate neurite extension. We report that EGF, in combination with KCl, stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of intracellular Ca2+ increases and not due to enhancement of MAP kinase activity over that seen with EGF alone. However, EGF plus KCl increased intracellular cAMP, and other cAMP elevating agents acted synergistically with EGF to promote neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked by inhibitors of transcription suggesting that synergistic regulation of transcription by the cAMP and MAP kinase pathways may stimulate neurite growth.
丝裂原活化蛋白激酶(MAP激酶)活性对于PC12细胞中生长因子诱导的神经突生长是必需的。尽管神经生长因子(NGF)和表皮生长因子(EGF)都能刺激MAP激酶活性,但EGF并不刺激神经突延伸。我们报告,EGF与氯化钾(KCl)联合使用时,可刺激PC12细胞的神经突生长。这种现象与细胞内钙离子(Ca2+)增加无关,也不是由于MAP激酶活性比单独使用EGF时增强所致。然而,EGF加KCl可增加细胞内环磷酸腺苷(cAMP),其他能提高cAMP水平的试剂与EGF协同作用以促进神经突生长。cAMP和EGF对神经突生长的刺激被转录抑制剂阻断,这表明cAMP和MAP激酶途径对转录的协同调节可能刺激神经突生长。