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	The p38 pathway provides negative feedback for Ras proliferative signaling
	Chen, G. ; Hitomi, M. ; Han, J. H. ; Stacey, D. W. ; Han JH(韩家淮)
	2000
关键词	ACTIVATED PROTEIN-KINASE NIH 3T3 CELLS MAP KINASE C-JUN TRANSCRIPTIONAL ACTIVATION CELLULAR-TRANSFORMATION INCREASING COMPLEXITY REGULATED KINASE-1/2 TOPOISOMERASE-II GENE-EXPRESSION
英文摘要	Ras activates three mitogen-activated protein kinases (MAPKs) including ERK, JNK and p38. Whereas the essential roles of ERK and JNK in Ras signaling has been established, the contribution of p38 remains unclear. Here we demonstrate that the p38 pathway functions as a negative regulator of Pas proliferative signaling via a feedback mechanism. Oncogenic Ras activated p38 and two p38-activated protein kinases, MAPK-activated protein kinase 2 (MK2) and p58-related/activated protein kinase (PRAK). MK2 and PRAK in turn suppressed Pas-induced gene expression and cell proliferation, whereas two mutant PRAKs, unresponsive to has, had little effect. Moreover, the constitutive p38 activator MKK6 also suppressed Pas activity in a p38-dependent manner whereas arsenite, a potent chemical inducer of p38, inhibited proliferation only in a tumor cell line that required Pas activity. MEK was required for Ras stimulation of the p38 pathway. The p38 pathway inhibited Pas activity by blocking activation of JNK, without effect upon ERK, as evidenced by the fact that PRAK-mediated suppression of Pas-induced cell proliferation was reversed by coexpression of JNKK2 or JNK1. These studies thus establish a negative feedback mechanism by which Pas proliferative activity is regulated via signaling integrations of MAPK pathways.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65843]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Chen, G.,Hitomi, M.,Han, J. H.,et al. The p38 pathway provides negative feedback for Ras proliferative signaling[J],2000.
APA	Chen, G.,Hitomi, M.,Han, J. H.,Stacey, D. W.,&韩家淮.(2000).The p38 pathway provides negative feedback for Ras proliferative signaling..
MLA	Chen, G.,et al."The p38 pathway provides negative feedback for Ras proliferative signaling".(2000).

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