PubMed Journals: J Biol Chem

  Source:		PMID: 10521483

    		J Biol Chem. 1999 Oct 22;274(43):30896-905.
			Identification of Tek/Tie2 binding partners.
			Binding to a multifunctional docking site
			mediates cell survival and migration.

			Jones N(1), Master Z, Jones J, Bouchard
			D, Gunji Y, Sasaki H, Daly R, Alitalo K,
			Dumont DJ.

			Author Information
			(1) Division of Cancer Biology Research,
			Sunnybrook and Women's College Health Sciences
			Centre, University of Toronto, Toronto,
			Ontario M4N 3M5.

			The Tek/Tie2 receptor tyrosine kinase plays
			a pivotal role in vascular and hematopoietic
			development. To study the signal transduction
			pathways that are mediated by this receptor,
			we have used the yeast two-hybrid system
			to identify signaling molecules that associate
			with the phosphorylated Tek receptor. Using
			this approach, we demonstrate that five
			molecules, Grb2, Grb7, Grb14, Shp2, and
			the p85 subunit of phosphatidylinositol
			3-kinase can interact with Tek in a
			phosphotyrosine-dependent manner through
			their SH2 domains. Mapping of the binding
			sites of these molecules on Tek reveals
			the presence of a multisubstrate docking
			site in the carboxyl tail of Tek (Tyr(1100)).
			Mutation of this site abrogates binding
			of Grb2 and Grb7 to Tek in vivo, and this
			site is required for tyrosine phosphorylation
			of Grb7 and p85 in vivo. Furthermore, stimulation
			of Tek-expressing cells with Angiopoietin-1
			results in phosphorylation of both Tek and
			p85 and in activation of endothelial cell
			migration and survival pathways that are
			dependent in part on phosphatidylinositol
			3-kinase. Taken together, these results
			demonstrate that Angiopoietin-1-induced
			signaling from the Tek receptor is mediated
			by a multifunctional docking site that is
			responsible for activation of both cell
			migration and cell survival pathways.

			PMID: 10521483 [Indexed for MEDLINE]

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