Dikic I, Dikic I, Schlessinger J
Ludwig Institute for Cancer Research, Uppsala, S-75124, Sweden.
J Biol Chem. 1998 Jun 5;273(23):14301-8. doi: 10.1074/jbc.273.23.14301.
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.
Pyk2是一种蛋白质酪氨酸激酶，它将G蛋白偶联受体、炎性细胞因子和细胞外刺激（这些刺激会提高细胞内钙浓度）与丝裂原活化蛋白激酶途径的激活以及离子通道功能的调节联系起来。在此，我们描述了一种通过可变RNA剪接产生的新型Pyk2亚型（Pyk2-H）的鉴定、克隆和特性。Pyk2-H主要在包括T细胞、B细胞和自然杀伤细胞在内的造血细胞中表达。T细胞或B细胞抗原受体的激活会导致Pyk2-H迅速发生酪氨酸磷酸化。在T细胞中，趋化因子RANTES和巨噬细胞炎性蛋白-1β也能激活Pyk2-H。此外，我们发现含有Pyk2和Pyk2-H羧基末端的谷胱甘肽S-转移酶融合蛋白能与胸腺裂解物中一组不同的酪氨酸磷酸化蛋白结合。Pyk2-H在造血细胞中的特异性表达及其被抗原或趋化因子激活可能有助于产生宿主免疫反应中涉及的细胞类型特异性信号。
