Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402.
We established Jurkat transfectants that overexpress Pyk2 or its mutants, K457A (lysine 457 was mutated to alanine), Pyk2-Y402F (tyrosine 402 to phenylalanine), and Pyk2-Y881F to investigate the role of Pyk2 in T cell activation. Pyk2 as well as kinase-inactive Pyk2-K457A, was phosphorylated at tyrosine residues 402, 580, and 881 upon ... T cell antigen receptor cross-linking, indicating that these residues are phosphorylated by other tyrosine kinase(s). However, no tyrosine phosphorylation of Pyk2-Y402F was detected while more than 60% of the tyrosine phosphorylation was observed in Pyk2-Y881F. Pyk2-Y402F inhibited the activation of endogenous Pyk2. The degree of activation of both c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase but not extracellular signal-regulated protein kinase after concurrent ligation of T cell antigen receptor and CD28 was reduced by more than 50% in the clones expressing Pyk2-Y402F. Consistent with this inhibition, IL-2 production was significantly diminished in the Pyk2-Y402F-expressing clones. Furthermore, we found that Pyk2, when overexpressed, associates with Zap70 and Vav. Taken together, these findings suggest that Pyk2 is involved in the activation of T cells through its tyrosine 402.
Mesh Terms:
Antigens, CD28, Cell Cycle Proteins, Enzyme Activation, Focal Adhesion Kinase 2, Glutathione Transferase, Humans, Interleukin-2, JNK Mitogen-Activated Protein Kinases, Jurkat Cells, Lymphocyte Activation, MAP Kinase Kinase 4, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Mutation, Phosphorylation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, T-Lymphocytes, Transfection, Tyrosine, ZAP-70 Protein-Tyrosine Kinase, p38 Mitogen-Activated Protein Kinases
Antigens, CD28, Cell Cycle Proteins, Enzyme Activation, Focal Adhesion Kinase 2, Glutathione Transferase, Humans, Interleukin-2, JNK Mitogen-Activated Protein Kinases, Jurkat Cells, Lymphocyte Activation, MAP Kinase Kinase 4, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Mutation, Phosphorylation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, T-Lymphocytes, Transfection, Tyrosine, ZAP-70 Protein-Tyrosine Kinase, p38 Mitogen-Activated Protein Kinases
J. Biol. Chem.
Date: Jun. 30, 2000
PubMed ID: 10867021
View in: Pubmed Google Scholar
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