*nlm.life
			PubMed Journals: Oncogene

  Source:		PMID: 9872331


    		Oncogene. 1998 Dec 17;17(24):3157-67.
     
			Repression of Stat3 activity by activation
			of mitogen-activated protein kinase (MAPK).

			Jain N(1), Zhang T, Fong SL, Lim CP, Cao
			X.

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

			STAT proteins are activated by phosphorylation
			at specific tyrosine residue at the carboxy-terminus
			which is required for dimer-formation, nuclear
			translocation, DNA binding and transcriptional
			activity in cells treated with cytokines
			and growth factors. Recent studies have
			indicated that STATs are also phosphorylated
			by MAPK, or extracellular signal-regulated
			kinase (ERK) on serine. We investigated
			the role of ERK on the regulation of STAT
			activity. Here, we report that ERK2 activated
			by its upstream kinase, MEK1, represses
			Stat3 transcriptional activity induced by
			Src or Jak-2. To unravel the mechanism of
			repression, we further showed that Stat3
			DNA binding activity and its tyrosine
			phosphorylation are also inhibited under
			the same conditions. ERK2 phosphorylates
			Stat3 on three serine-containing peptides
			and decreases its tyrosine phosphorylation
			induced by EGF treatment. We also detected
			an association of ERK2 and Stat3 in vivo
			which is modulated positively by activation
			of ERK2, but negatively by Jak2. We propose
			that MAP kinase cascade may negatively regulate
			Stat3 activities by decreasing its tyrosine
			phosphorylation and also possibly by association.

			DOI: 10.1038/sj.onc.1202238 PMID: 9872331
			[Indexed for MEDLINE]

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