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	Rac1-MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells
	Han, Q. W. ; Leng, J. ; Bian, D. F. ; Mahanivong, C. ; Carpenter, K. A. ; Pan, Z. X. K. ; Han, J. H. ; Huang, S. ; Han JH(韩家淮)
	2002
关键词	MESSENGER-RNA STABILITY P38 MAP KINASE PROTEIN-KINASE BINDING PROTEIN RECEPTOR EXPRESSION SIGNAL-TRANSDUCTION CYCLE PROGRESSION MAMMALIAN-CELLS RICH ELEMENTS GROWTH
英文摘要	We reported previously that down-regulating or functionally blocking alphav integrins inhibits endogenous p38 mitogen-activated protein kinase (MAPK) activity and urokinase plasminogen activator (uPA) expression in invasive MDA-MB-231 breast cancer cells whereas engaging av integrins with vitronectin activates p38 MAPK and up-regulates uPA expression (Chen, J., Baskerville, C., Han, Q., Pan, Z., and Huang, S. (2001) J. Biol. Chem. 276, 47901-47905). Currently, it is not clear what upstream and downstream signaling molecules of p38 MAPK mediate alphav integrin-mediated uPA up-regulation. In the present study, we found that av integrin ligation activated small GTPase Rac1 preferentially, and dominant negative Rac1 inhibited av integrin-mediated p38 MAPK activation. Using constitutively active MAPK kinases, we found that both constitutively active MKK3 and MKK6 mutants were able to activate p38 MAPK and up-regulate uPA expression, but only dominant negative MKK3 blocked alphav integrin-mediated p38 MAPK activation and uPA up-regulation. These results suggest that MKK3, rather than MKK6, mediates av integrin-induced p38 MAPK activation. Among the potential downstream effectors of p38 MAPK, we found that only MAPK-activated protein kinase 2 affects alphav integrin-mediated uPA up-regulation significantly. Finally, using beta-globin reporter gene constructs containing uPA mRNA 3'-untranslated region (UTR) and adenosineturidine-rich elements-deleted 3'-UTR, we demonstrated that p38 MAPK/MAPK-activated protein kinase 2 signaling pathway regulated uPA mRNA stability through a mechanism involving the adenosine/uridine-rich elements sequence in 3'-UTR of uPA mRNA.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65836]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Han, Q. W.,Leng, J.,Bian, D. F.,et al. Rac1-MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells[J],2002.
APA	Han, Q. W..,Leng, J..,Bian, D. F..,Mahanivong, C..,Carpenter, K. A..,...&韩家淮.(2002).Rac1-MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells..
MLA	Han, Q. W.,et al."Rac1-MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells".(2002).

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