The Syk/ZAP-70 protein tyrosine kinase connection to antigen receptor signalling processes.
The T- and B-cell receptor (TCR and BCR) signal transduction processes involve a coordinated interplay between two classes of non-receptor protein tyrosine kinases (PTKs), the Src-family and the Syk/ZAP-70 family of PTKs. Following antigen-receptor stimulation, the Src-family of PTKs mediate the phosphorylation of tyrosine residues contained in a signalling motif localized in the TCR and BCR subunits. The phosphorylation of this signalling motif recruits the Syk/ZAP-70 family of PTKs into the antigen receptor complex. This mechanism requires the tandem SH2 domains in ZAP-70 complexing to two critically spaced phosphotyrosine residues within the signalling motif. The clustering of Syk/ZAP-70 and cross-talk between this family and the Src-PTKs regulates subsequent signalling events that lead to a variety of cellular responses, such as antibody secretion, lymphokine production, cytolytic activity, proliferation, differentiation and cell survival.
Department of Medicine, University of California, San Francisco 94143, USA.
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van Oers
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Weiss
D000595:Amino Acid Sequence; D000818:Animals; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human