Reconstitution of T cell antigen receptor-induced Erk2 kinase activation in Lck-negative JCaM1 cells by Syk.

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  • Additional Information
    • Source:
      Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE
    • Publication Information:
      Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
      Original Publication: Berlin, New York, Springer.
    • Subject Terms:
    • Abstract:
      The two related protein-tyrosine kinases Syk and Zap are rapidly phosphorylated on tyrosine residues and enzymatically activated upon crosslinking of the T cell antigen receptor. We have previously reported that the activation of Syk is less dependent on the Src family kinase Lck than the activation of Zap. Here we report that overexpression of Syk in the Lck-negative JCaM1 cells enabled the T cell antigen receptor/CD3 complex to induce a normal activation of the mitogen-activated protein kinase (MAPK) pathway and expression of a nuclear factor of activated T cells reporter construct. In contrast, Zap and other protein-tyrosine kinases were unable to reconstitute these signaling pathways when expressed at the same levels. In parallel, Syk was phosphorylated on tyrosine, while Zap was not. The Syk-mediated T cell antigen receptor-induced MAPK activation was detectable within 1 min of receptor stimulation and peaked at 3-5 min. The capacity of Syk to reconstitute the MAPK response required the catalytic activity of Syk, an intact autophosphorylation site (Y518 and Y519), both Src homology 2 domains and it was blocked by the inhibitory N17-mutated dominant-negative Ras construct. A Y341-->F mutant of Syk, which is deficient in its interaction with phospholipase Cy1 and Vav, was less efficient than wild-type Syk. Our results suggest that Syk, in contrast to Zap, can transduce signals from the T cell antigen receptor independently of Lck.
    • Grant Information:
      AI35603 United States AI NIAID NIH HHS; CA35799 United States CA NCI NIH HHS; GM48960 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (Enzyme Precursors)
      0 (Intracellular Signaling Peptides and Proteins)
      0 (NFATC Transcription Factors)
      0 (Nuclear Proteins)
      0 (Oncogene Proteins, Viral)
      0 (Receptors, Antigen, T-Cell)
      0 (Transcription Factors)
      42HK56048U (Tyrosine)
      47E5O17Y3R (Phenylalanine)
      EC 1.13.12.- (Luciferases)
      EC 2.7.10.1 (Protein-Tyrosine Kinases)
      EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
      EC 2.7.10.2 (SYK protein, human)
      EC 2.7.10.2 (Syk Kinase)
      EC 2.7.10.2 (src-Family Kinases)
      EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
    • Publication Date:
      Date Created: 19970401 Date Completed: 19970529 Latest Revision: 20190620
    • Publication Date:
      20231215
    • Accession Number:
      10.1111/j.1432-1033.1997.00084.x
    • Accession Number:
      9128727