Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis
Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis
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DOI：
10.1111/j.1365-2567.2004.01822.x
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发表时间：
2004-04-01
期刊：
影响因子：
6.4
通讯作者：
Bertini, R
中科院分区：
文献类型：
--
作者：
Di Cioccio, V;Strippoli, R;Bertini, R
导致CXCL 8/IL-8诱导的人类中性粒细胞迁移的信号通路尚未得到充分表征。本研究表明，CXCL 8诱导酪氨酸磷酸化以及富含脯氨酸的酪氨酸激酶2（Pyk 2），非受体蛋白酪氨酸激酶（PTK），在人类中性粒细胞的酶活性。CXCL 8诱导Pyk 2酪氨酸磷酸化受Src PTK激活调节，而不受磷脂酰肌醇3-激酶激活影响。Src PTK抑制剂PP 1对Pyk 2活化的抑制作用通过抑制CXCL 8介导的中性粒细胞趋化性而被抑制。在CXCL 8受体中，Src蛋白酪氨酸激酶激活选择性调节CXCR 1介导的多形核中性粒细胞（PMN）趋化性。Pyk 2的激酶死亡突变体PykM的过表达阻断了CXCL 8诱导的HL-60来源的PMN样细胞的趋化性，从而确定了Pyk 2在CXCL 8诱导的趋化性中的关键作用。
The signalling pathways leading to CXCL8/IL-8-induced human neutrophil migration have not been fully characterized. The present study demonstrates that CXCL8 induces tyrosine phosphorylation as well as enzymatic activity of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor protein tyrosine kinase (PTK), in human neutrophils. Induction of Pyk2 tyrosine phosphorylation by CXCL8 is regulated by Src PTK activation, whereas it is unaffected by phosphatidylinositol 3-kinase activation. Inhibition of Pyk2 activation by PP1, a Src PTK inhibitor, is paralleled by the inhibition of CXCL8-mediated neutrophil chemotaxis. Among CXCL8 receptors, Src protein tyrosine kinase activation selectively regulates CXCR1-mediated polymorphonuclear neutrophil (PMN) chemotaxis. Overexpression of PykM, the kinase-dead mutant of Pyk2, blocks CXCL8-induced chemotaxis of HL-60-derived PMN-like cells, thus pinpointing the key role of Pyk2 in CXCL8-induced chemotaxis.