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			PubMed Journals: J Biol Chem

  Source:		PMID: 10521505


    		J Biol Chem. 1999 Oct 22;274(43):31055-61.
     
			Serine phosphorylation and negative regulation
			of Stat3 by JNK.

			Lim CP(1), Cao X.

			Author Information
			(1) Signal Transduction Laboratory, Institute
			of Molecular and Cell Biology, National
			University of Singapore, Singapore 117609.

			STATs are activated by various cytokines and
			growth factors via tyrosine phosphorylation,
			which leads to sequential dimer formation,
			nuclear translocation, binding to specific
			DNA sequences, and regulation of gene expression.
			Recently, serine phosphorylation of Stat3
			on Ser-727 by ERK has been identified in
			response to epidermal growth factor (EGF).
			Here, we report that Ser-727 phosphorylation
			of Stat3 can also be induced by JNK and
			activated either by stress or by its upstream
			kinase and that various stress treatments
			induce serine phosphorylation of Stat3 in
			the absence of tyrosine phosphorylation.
			Inhibitors of ERK and p38 did not inhibit
			UV-induced Stat3 serine phosphorylation,
			suggesting that neither of them is involved.
			We further demonstrate that JNK1, activated
			by its upstream kinase MKK7, negatively
			regulated the tyrosine phosphorylation and
			DNA binding and transcriptional activities
			of Stat3 stimulated by EGF. Correspondingly,
			pretreatment of cells with UV reduced the
			EGF-stimulated tyrosine phosphorylation
			and phosphotyrosine-dependent activities
			of Stat3. The inhibitory effect was not
			observed for Stat1. Our results suggest
			that Stat3 is a target of JNK that may regulate
			Stat3 activity via both Ser-727
			phosphorylation-dependent and -independent
			mechanisms.

			PMID: 10521505 [Indexed for MEDLINE]

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