PubMed Journals: J Biol Chem

  Source:		PMID: 12624099

    		J Biol Chem. 2003 May 16;278(20):18440-7.
     		Epub 2003 Mar 6.

			Adipose-specific expression, phosphorylation
			of Ser794 in insulin receptor substrate-1,
			and activation in diabetic animals of
			salt-inducible kinase-2.

			Horike N(1), Takemori H, Katoh Y, Doi J,
			Min L, Asano T, Sun XJ, Yamamoto H, Kasayama
			S, Muraoka M, Nonaka Y, Okamoto M.

			Author Information
			(1) Department of Biochemistry and Molecular
			Biology, Graduate School of Medicine,
			Osaka University, 2-2 Yamadaoka, Suita,
			Osaka 565-0871, Japan.

			Salt-inducible kinase (SIK), first cloned
			from the adrenal glands of rats fed a high
			salt diet, is a serine/threonine protein
			kinase belonging to an AMP-activated protein
			kinase family. Induced in Y1 cells at an
			early stage of ACTH stimulation, it regulated
			the initial steps of steroidogenesis. Here
			we report the identification of its isoform
			SIK2. When a green fluorescent protein-fused
			SIK2 was expressed in 3T3-L1 preadipocytes,
			it was mostly present in the cytoplasm.
			When coexpressed in cAMP-responsive element-reporter
			assay systems, SIK2 could repress the
			cAMP-responsive element-dependent transcription,
			although the degree of repression seemed
			weaker than that by SIK1. SIK2 was specifically
			expressed in adipose tissues. When 3T3-L1
			cells were treated with the adipose differentiation
			mixture, SIK2 mRNA was induced within 1
			h, the time of induction almost coinciding
			with that of c/EBPbeta mRNA. Coexpressed with
			human insulin receptor substrate-1 (IRS-1)
			in COS cells, SIK2 could phosphorylate Ser(794)
			of human IRS-1. Adenovirus-mediated overexpression
			of SIK2 in adipocytes elevated the level
			of phosphorylation at Ser(789), the mouse
			equivalent of human Ser(794). Moreover,
			the activity and content of SIK2 were elevated
			in white adipose tissues of db/db diabetic
			mice. These results suggest that highly
			expressed SIK2 in insulin-stimulated adipocytes
			phosphorylates Ser(794) of IRS-1 and, as
			a result, might modulate the efficiency
			of insulin signal transduction, eventually
			causing the insulin resistance in diabetic

			DOI: 10.1074/jbc.M211770200 PMID: 12624099
			[Indexed for MEDLINE]

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