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			PubMed Journals: Cell

  Source:		PMID: 8221888


    		Cell. 1993 Nov 5;75(3):487-93.
     
			MKP-1 (3CH134), an immediate early gene
			product, is a dual specificity phosphatase
			that dephosphorylates MAP kinase in vivo.

			Sun H(1), Charles CH, Lau LF, Tonks NK.

			Author Information
			(1) Cold Spring Harbor Laboratory, New York
			11724-2208.

			Mitogenic stimulation of cells induces rapid
			and transient activation of MAP kinases.
			Here we report that a growth factor-inducible
			gene, 3CH134, encodes a dual specificity
			phosphatase that dephosphorylates and inactivates
			p42MAPK both in vitro and in vivo. In vitro,
			3CH134 protein dephosphorylates both T183
			and Y185 in p42MAPK. In serum-stimulated
			normal fibroblasts, the kinetics of inactivation
			of p42MAPK coincides with the appearance
			of newly synthesized 3CH134 protein, and
			the protein synthesis inhibitor cycloheximide
			leads to persistent activation of MAP kinase.
			Expression of 3CH134 in COS cells leads
			to selective dephosphorylation of p42MAPK
			from the spectrum of phosphotyrosyl proteins.
			3CH134 blocks phosphorylation and activation
			of p42MAPK mediated by serum, oncogenic
			Ras, or activated Raf, whereas the catalytically
			inactive mutant of the phosphatase, Cys-258-->Ser,
			augments MAP kinase phosphorylation under
			similar conditions. The mutant 3CH134 protein
			also forms a physical complex with the
			phosphorylated form of p42MAPK. These findings
			suggest that 3CH134 is a physiological MAP
			kinase phosphatase; we propose the name
			MKP-1 for this phosphatase.

			PMID: 8221888 [Indexed for MEDLINE]

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