Cell cycle arrest mediated by the MEK/mitogen-activated protein kinase pathway
作者： K. M. Pumiglia , S. J. Decker
关键词:
摘要: The mitogen-activated protein kinase (MAPK) cascade plays a crucial role in the transduction of extracellular signals into responses governing growth and differentiation. effects specific inhibitor MAPK (MEK)/MAPK pathway (PD98059) on nerve factor (NGF)-induced arrest inhibition cell cycle-dependent kinases (CDKs) have been examined. Treatment NIH 3T3 cells expressing TRKA with PD98059 dramatically reversed complete these caused by NGF. also blocked ability NGF to inhibit activities CDK4 CDK2, while partially preventing induction p21Cip1/WAF1. To independently evaluate involvement MEK/MAPK arrest, an inducible activated form Raf-1 protooncogene (ΔRAF-1:ER) was expressed cells. Activation ΔRAF-1:ER resulted prolonged increase activity cells, concomitant p21Cip1/WAF1 CDK2 activity. These activation were all treatment PD98059. data indicate that addition functioning as positive effector growth, stimulation can result CDK cycle arrest.
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