Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor signaling.
Pyk2 is a protein tyrosine kinase that links G-protein-coupled receptors, inflammatory cytokines, and extracellular stimuli that elevate intracellular calcium concentration with activation of the mitogen-activated protein kinase pathways and regulation of ion channel functions. Here we describe the identification, cloning, and characterization of a new isoform of Pyk2 (Pyk2-H) that is generated by alternative RNA splicing. Pyk2-H is mainly expressed in hematopoietic cells including T-cells, B-cells, and natural killer cells. Engagement of T-cell or B-cell antigen receptors leads to rapid tyrosine phosphorylation of Pyk2-H. Pyk2-H is also activated in response to the chemokines RANTES and macrophage inflammatory protein-1beta in T cells. In addition, we show that glutathione S-transferase fusion proteins containing the carboxyl termini of Pyk2 and Pyk2-H bind to a different set of tyrosine-phosphorylated proteins in thymus lysates. Specific expression of Pyk2-H and its activation by antigens or chemokines in hematopoietic cells may contribute toward the generation of cell type-specific signals involved in host immune responses.
Dikic
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I
Ludwig Institute for Cancer Research, Uppsala, S-75124, Sweden. Ivan.Dikic@licr.uu.se
Dikic
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I
Schlessinger
J
J
D017398:Alternative Splicing / Q000235:genetics; D000941:Antigens / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000502:physiology; D018925:Chemokines / Q000494:pharmacology*; D003001:Cloning, Molecular; D051418:Focal Adhesion Kinase 2; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018922:HL-60 Cells; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry*; D016296:Mutagenesis / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
D000941:Antigens; D018925:Chemokines; D007527:Isoenzymes; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; C112947:protein tyrosine kinase Pyk2-H; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2