PubMed Journals: Oncogene

  Source:		PMID: 9632142

    		Oncogene. 1998 May;16(20):2657-70.
			Complex formation between EphB2 and Src
			requires phosphorylation of tyrosine 611
			in the EphB2 juxtamembrane region.

			Zisch AH(1), Kalo MS, Chong LD, Pasquale

			Author Information
			(1) The Burnham Institute, La Jolla, California
			92037, USA.

			The cellular components of the neuronal
			signaling pathways of Eph receptor tyrosine
			kinases are only beginning to be elucidated.
			Here we show that in vivo tyrosine phosphorylation
			sites of the Eph receptors EphA3, EphA4,
			and EphB2 in embryonic retina serve as binding
			sites for the Src-homology 2 (SH2) domain
			of Src kinase. Furthermore, tyrosine-phosphorylated
			EphB2 was detected in Src immunoprecipitates
			from transfected Cos cells, indicating that
			EphB2 and Src can physically associate.
			Interestingly, a form of Src with reduced
			electrophoretic mobility and increased tyrosine
			phosphorylation was detected in Cos cells
			expressing tyrosine-phosphorylated EphB2,
			suggesting a functional interaction between
			EphB2 and Src. Yeast two-hybrid analysis
			in conjunction with site-directed mutagenesis
			demonstrated that phosphorylated tyrosine
			611 in the juxtamembrane region of EphB2
			is crucial for the interaction with the
			SH2 domain of Src. In contrast, binding
			of the carboxy-terminal SH2 domain of phospholipase
			Cgamma was not abolished upon mutation of
			tyrosine 611 in EphB2. Phosphopeptide mapping
			of autophosphorylated full-length EphB2,
			and wild-type and tyrosine to phenylalanine
			mutants of the EphB2 cytoplasmic domain
			fused to LexA, showed tyrosine 611 in the
			sequence motif YEDP as a major site of
			autophosphorylation in EphB2. Our mutational
			analysis also indicated that tyrosines 605
			and 611 are important for EphB2 kinase activity.
			We propose Src kinase as a downstream effector
			that mediates the neuron's response to Eph
			receptor activation.

			DOI: 10.1038/sj.onc.1201823 PMID: 9632142
			[Indexed for MEDLINE]

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