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			PubMed Journals: J Biol Chem

  Source:		PMID: 11707464


    		J Biol Chem. 2002 Jan 25;277(4):2573-8.
     		Epub 2001 Nov 13.

			Akt (protein kinase B) negatively regulates
			SEK1 by means of protein phosphorylation.

			Park HS(1), Kim MS, Huh SH, Park J, Chung
			J, Kang SS, Choi EJ.

			Author Information
			(1) National Creative Research Initiative
			Center for Cell Death, Graduate School of
			Biotechnology, Korea University, Seoul 136-701,
			Korea.

			The protein serine-threonine kinase Akt mediates cell
			survival signaling initiated by various
			growth-promoting factors such as insulin.
			Here we report that SEK1 is a target of
			Akt in intact cells. Insulin inhibited the
			anisomycin-induced stimulation of both endogenous
			SEK1 and its substrate c-Jun N-terminal kinase
			(JNK), but not that of the upstream kinase
			MEKK1, in 293T cells. The inhibitory action
			of insulin on SEK1 or JNK1 activation was
			prevented by the phosphatidylinositol 3-kinase
			inhibitor LY294002. Expression of a constitutively
			active form of Akt also inhibited both SEK1
			and JNK1 activation, but not that of MEKK1,
			in transfected 293T cells. Co-immunoprecipitation
			analysis revealed that endogenous Akt physically
			interacted with endogenous SEK1 in cells
			and that this interaction was promoted by
			insulin. In vitro and in vivo (32)P labeling
			indicated that Akt phosphorylated SEK1 on
			serine 78. The SEK1 mutant SEK1(S78A) was
			resistant to Akt-induced inhibition. Finally,
			activated Akt inhibited SEK1-mediated apoptosis,
			and this effect of Akt was prevented by
			overexpression of SEK(S78A). Taken together,
			these results suggest that Akt suppresses
			stress-activated signaling by targeting
			SEK1.

			DOI: 10.1074/jbc.M110299200 PMID: 11707464
			[Indexed for MEDLINE]

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