PubMed Journals: J Biol Chem

  Source:		PMID: 9685404

    		J Biol Chem. 1998 Aug 7;273(32):20487-93.
			Tyrosine 474 of ZAP-70 is required for association
			with the Shc adaptor and for T-cell antigen
			receptor-dependent gene activation.

			Pacini S(1), Ulivieri C, Di Somma MM, Isacchi
			A, Lanfrancone L, Pelicci PG, Telford JL,
			Baldari CT.

			Author Information
			(1) Department of Evolutionary Biology,
			University of Siena, Via Mattioli 4, 53100
			Siena, Italy.

			The protein tyrosine kinase ZAP-70 plays
			a central role in T-cell activation. Following
			receptor engagement, ZAP-70 is recruited
			to the phosphorylated subunits of the T-cell
			antigen receptor (TCR). This event results
			in ZAP-70 activation and in association
			of ZAP-70 with a number of signaling proteins.
			Among these is the Shc adaptor, which couples
			the activated TCR to Ras. Shc interaction
			with ZAP-70 is mediated by the Shc PTB domain.
			The inhibitory effect of a Shc mutant containing
			the isolated PTB domain suggests that Shc
			interaction with ZAP-70 might be required
			for TCR signaling. Here, we show that a
			point mutation (Phe474) of the putative
			Shc binding site on ZAP-70, spanning tyrosine
			474, prevented ZAP-70 interaction with Shc
			and the subsequent binding of Shc to phospho-zeta.
			Neither ZAP-70 catalytic activity nor the
			pattern of protein phosphorylation induced
			by TCR triggering was affected by this mutation.
			However expression of the Phe474 ZAP-70
			mutant resulted in impaired TCR-dependent
			gene activation. ZAP-70 could effectively
			phosphorylate Shc in vitro. Only the CH
			domain, which contains the two Grb2 binding
			sites on Shc, was phosphorylated by ZAP-70.
			Both Grb2 binding sites were excellent substrates
			for ZAP-70. The data show that Tyr474 on
			ZAP-70 is required for TCR signaling and
			suggest that Shc association with ZAP-70
			and the resulting phosphorylation of Shc
			might be an obligatory step in linking the
			activated TCR to the Ras pathway.

			PMID: 9685404 [Indexed for MEDLINE]

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