PubMed Journals: Mol Cell Biol

  Source:		PMID: 9111318

    		Mol Cell Biol. 1997 May;17(5):2497-501.
			Activation of Jak2 catalytic activity requires
			phosphorylation of Y1007 in the kinase activation

			Feng J(1), Witthuhn BA, Matsuda T, Kohlhuber
			F, Kerr IM, Ihle JN.

			Author Information
			(1) Department of Biochemistry,
			St. Jude Children's Research Hospital,
			Memphis, Tennessee 38105, USA.

			The Janus protein tyrosine kinases (Jaks)
			play critical roles in transducing growth
			and differentiation signals emanating from
			ligand-activated cytokine receptor complexes.
			The activation of the Jaks is hypothesized
			to occur as a consequence of auto- or
			transphosphorylation on tyrosine residues
			associated with ligand-induced aggregation
			of the receptor chains and the associated
			Jaks. In many kinases, regulation of catalytic
			activity by phosphorylation occurs on residues
			within the activation loop of the kinase
			domain. Within the Jak2 kinase domain, there
			is a region that has considerable sequence
			homology to the regulatory region of the
			insulin receptor and contains two tyrosines,
			Y1007 and Y1008, that are potential regulatory
			sites. In the studies presented here, we
			demonstrate that among a variety of sites,
			Y1007 and Y1008 are sites of trans- or
			autophosphorylation in vivo and in in vitro
			kinase reactions. Mutation of Y1007, or
			both Y1007 and Y1008, to phenylalanine essentially
			eliminated kinase activity, whereas mutation
			of Y1008 to phenylalanine had no detectable
			effect on kinase activity. The mutants were
			also examined for the ability to reconstitute
			erythropoietin signaling in gamma2 cells,
			which lack Jak2. Consistent with the kinase
			activity, mutation of Y1007 to phenylalanine
			eliminated the ability to restore signaling.
			Moreover, phosphorylation of a kinase-inactive
			mutant (K882E) was not detected, indicating
			that Jak2 activation during receptor aggregation
			is dependent on Jak2 and not another
			receptor-associated kinase. The results
			demonstrate the critical role of phosphorylation
			of Y1007 in Jak2 regulation and function.

			PMCID: PMC232098 PMID: 9111318 [Indexed
			for MEDLINE]

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