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Titolo:
ZAP-70 BINDING-SPECIFICITY TO T-CELL RECEPTOR TYROSINE-BASED ACTIVATION MOTIFS - THE TANDEM SH2 DOMAINS OF ZAP-70 BIND DISTINCT TYROSINE-BASED ACTIVATION MOTIFS WITH VARYING AFFINITY
Autore:
ISAKOV N; WANGE RL; BURGESS WH; WATTS JD; AEBERSOLD R; SAMELSON LE;
Indirizzi:
NICHHD,CELL BIOL & METAB BRANCH BETHESDA MD 20892 NICHHD,CELL BIOL & METAB BRANCH BETHESDA MD 20892 BEN GURION UNIV NEGEV,DEPT MICROBIOL & IMMUNOL IL-84105 BEER SHEVA ISRAEL BEN GURION UNIV NEGEV,CANC RES CTR IL-84105 BEER SHEVA ISRAEL AMER RED CROSS,HOLLAND MED LAB ROCKVILLE MD 20850 UNIV BRITISH COLUMBIA,BIOMED RES CTR VANCOUVER BC V6T 1Z3 CANADA
Titolo Testata:
The Journal of experimental medicine
fascicolo: 1, volume: 181, anno: 1995,
pagine: 375 - 380
SICI:
0022-1007(1995)181:1<375:ZBTTRT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIGEN RECEPTOR; ZETA-CHAIN; KINASE; CD3-EPSILON; COMPONENTS; COMPLEX; TAIL;
Tipo documento:
Note
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
N. Isakov et al., "ZAP-70 BINDING-SPECIFICITY TO T-CELL RECEPTOR TYROSINE-BASED ACTIVATION MOTIFS - THE TANDEM SH2 DOMAINS OF ZAP-70 BIND DISTINCT TYROSINE-BASED ACTIVATION MOTIFS WITH VARYING AFFINITY", The Journal of experimental medicine, 181(1), 1995, pp. 375-380

Abstract

Engagement of the T cell antigen receptor (TCR) results in activationof several tyrosine kinases leading to tyrosine phosphorylation of protein substrates and activation of multiple biochemical pathways. TCR-mediated activation of the src-family kinases, Lck and Fyn, results intyrosine phosphorylation of the TCR zeta and CD3 chains. The site of phosphorylation in these chains is the tyrosine-based activation motif(TAM), a 15-16 amino acid module containing two tyrosine residues. Tyrosine-phosphorylated TAMs serve as targets for binding of the zeta-associated protein (ZAP-70) tyrosine kinase via its tandem SH2 domains. This binding correlates with activation of ZAP-70, a critical event in T cell activation. To further define the structural requirements for ZAP-70 interaction with the TCR, we developed a binding assay using immobilized glutathione S-transferase fusion proteins containing the NH2-and/or COOH-terminal SH2 domains of ZAP-70, and soluble synthetic peptides with the sequence of the cytoplasmic region of the TCR zeta chain (TCRS zeta(cyt) or individual TCR zeta and CD3 epsilon TAM motifs. Direct binding studies demonstrated that the tandem ZAP-70 SH2 domains bind phosphorylated, but not nonphosphorylated, TCR zeta(cyt). The NH2-terminal ZAP-70 SH2 domain also binds to TCR zeta(cyt) but with 100-fold lower affinity. No binding was observed with the COOH-terminal ZAP-70 SH2 domain. Similar studies demonstrated that the ZAP-70 tandem SH2 domain can bind a TCR zeta(3) TAM peptide in which both tyrosine residues are phosphorylated: Little or no binding was observed with peptides phosphorylated at only one tyrosine residue, or a nonphosphorylated peptide. Binding of the tandem SH2 domains to the other two TCR zetaTAM peptides and to a CD3 epsilon TAM peptide was also observed. AIL four doubly tyrosine phospholylated TAM peptides cross-compete with each other for binding to the tandem SH2 domains of ZAP-70. The affinityof these peptides for the tandem SH2 construct demonstrated a hierarchy of TAM zeta 1 greater than or equal to TAM zeta(2) > TAM epsilon greater than or equal to TAM zeta(3). The results provide further evidence that the ZAP-70 interaction with the TCR requires prior phosphorylation of both tyrosine residues within a TAM motif. Binding of ZAP-70 to phospho-TAMs is notable for the high level of cooperativity between the two SH2 domains, which individually demonstrate low affinity interaction with the ligand. The cooperativity ensures higher affinity for the doubly phosphorylated ligand. Affinity differences of as much as 30-fold indicates a significant specificity of interaction of ZAP-70 SH2 domains for different phospho-TAMs.

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Documento generato il 27/11/20 alle ore 07:33:48