PubMed Journals: J Biol Chem

  Source:		PMID: 7592979

    		J Biol Chem. 1995 Nov 10;270(45):27213-21.
			Constitutive activation of mitogen-activated
			protein kinase-activated protein kinase
			2 by mutation of phosphorylation sites and
			an A-helix motif.

			Engel K(1), Schultz H, Martin F, Kotlyarov
			A, Plath K, Hahn M, Heinemann U, Gaestel

			Author Information
			(1) Max-Delbrück-Centrum für Molekulare
			Medizin, Berlin, Federal Republic of Germany.

			A recently described downstream target of
			mitogen-activated protein kinases (MAPKs)
			is the MAPK-activated protein (MAPKAP) kinase
			2 which has been shown to be responsible
			for small heat shock protein phosphorylation.
			We have analyzed the mechanism of MAPKAP
			kinase 2 activation by MAPK phosphorylation
			using a recombinant MAPKAP kinase 2-fusion
			protein, p44MAPK and p38/40MAPK in vitro
			and using an epitope-tagged MAPKAP kinase
			2 in heat-shocked NIH 3T3 cells. It is demonstrated
			that, in addition to the known phosphorylation
			of the threonine residue carboxyl-terminal
			to the catalytic domain, Thr-317, activation
			of MAPKAP kinase 2 in vitro and in vivo
			is dependent on phosphorylation of a second
			threonine residue, Thr-205, which is located
			within the catalytic domain and which is
			highly conserved in several protein kinases.
			Constitutive activation of MAPKAP kinase
			2 is obtained by replacement of both of
			these threonine residues by glutamic acid.
			A constitutively active form of MAPKAP kinase
			2 is also obtained by deletion of a
			carboxyl-terminal region containing Thr-317
			and the A-helix motif or by replacing the
			conserved residues of the A-helix. These
			data suggest a dual mechanism of MAPKAP
			kinase 2 activation by phosphorylation of
			Thr-205 inside the catalytic domain and
			by phosphorylation of Thr-317 outside the
			catalytic domain involving an autoinhibitory
			A-helix motif.

			PMID: 7592979 [Indexed for MEDLINE]

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