Yao H, Labudda K, Rim C, Capodieci P, Loda M, Stork P J
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
J Biol Chem. 1995 Sep 1;270(35):20748-53. doi: 10.1074/jbc.270.35.20748.
The rat pheochromocytoma (PC12) cell line is a model for studying the mechanism of growth factor action. Both epidermal growth factor and nerve growth factor stimulate mitogen-activated protein (MAP) kinase in these cells. Recent data suggest that the transient activation of MAP kinase may trigger proliferation, whereas sustained activation triggers differentiation in these cells. We have tested this model by asking whether agents that stimulate MAP kinase without inducing differentiation can act additively to trigger differentiation. Neither forskolin nor epidermal growth factor can stimulate differentiation, yet both activate MAP kinase in these cells. Together, their actions on MAP kinase are synergistic. Cells treated with both agents differentiate, measured morphologically and by the induction of neural-specific genes. We propose that cellular responses to growth factor action are dependent not only on the activation of growth factor receptors by specific growth factors but on synchronous signals that may elevate MAP kinase levels within the same cells.
大鼠嗜铬细胞瘤（PC12）细胞系是研究生长因子作用机制的模型。表皮生长因子和神经生长因子均可刺激这些细胞中的丝裂原活化蛋白（MAP）激酶。最近的数据表明，MAP激酶的瞬时激活可能触发细胞增殖，而持续激活则触发这些细胞的分化。我们通过询问在不诱导分化的情况下刺激MAP激酶的试剂是否能累加作用以触发分化来测试该模型。福斯可林和表皮生长因子均不能刺激分化，但二者均可激活这些细胞中的MAP激酶。它们对MAP激酶的作用是协同的。用这两种试剂处理的细胞发生分化，这通过形态学测量以及神经特异性基因的诱导来确定。我们提出，细胞对生长因子作用的反应不仅取决于特定生长因子对生长因子受体的激活，还取决于可能提高同一细胞内MAP激酶水平的同步信号。
