Evidence of ζ protein kinase C involvement in polymorphonuclear neutrophil integrin-dependent adhesion and chemotaxis
Evidence of ζ protein kinase C involvement in polymorphonuclear neutrophil integrin-dependent adhesion and chemotaxis
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DOI：
10.1074/jbc.273.46.30306
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发表时间：
1998-11-13
影响因子：
4.8
通讯作者：
Butcher, EC
中科院分区：
文献类型：
--
作者：
Laudanna, C;Mochly-Rosen, D;Butcher, EC
经典的趋化因子和趋化因子触发血液白细胞与血管内皮的整合素依赖性粘附，并指导随后的外渗和迁移到组织中。在人类多形核白细胞对甲酰肽和白细胞介素8的反应的研究中，我们发现非典型zeta蛋白激酶C参与导致趋化因子触发的肌动蛋白组装、整合素依赖性粘附和趋化性的信号通路的证据。经典和新型蛋白激酶C同工酶的选择性抑制剂不能阻止趋化因子诱导的中性粒细胞粘附和趋化。相比之下，白屈菜红碱氯化物和合成的肉豆蔻酰化肽与内源性ζ蛋白激酶C假底物区域的基础上的序列块激动剂诱导的粘附纤维蛋白原，趋化性和F-肌动蛋白积累。生化分析表明，化学引诱物触发zeta蛋白激酶C快速易位到质膜，伴随着激酶活性的快速但短暂的增加。此外，用C3转移酶（Rho小GTP酶的特异性抑制剂）预处理可阻断zeta蛋白激酶C质膜转位，但不阻断α蛋白激酶C质膜转位。来自zeta蛋白激酶C的合成肽也抑制佛波酯诱导的整合素依赖性粘附，但不抑制NADPH氧化酶活化，C3转移酶预处理阻断佛波酯触发的zeta易位，但不抑制α-谷氨酰胺转运。蛋白激酶C这些数据表明zeta蛋白激酶C参与趋化因子诱导的白细胞整合素依赖性粘附和趋化。此外，他们强调了非典型蛋白激酶C同工酶和Rho信号通路之间的潜在联系，导致整合素激活。
Classical chemoattractants and chemokines trigger integrin-dependent adhesion of blood leukocytes to vascular endothelium and also direct subsequent extravasation and migration into tissues. In studies of human polymorphonuclear neutrophil responses to formyl peptides and to interleukin 8, we show evidence of involvement of the atypical zeta protein kinase C in the signaling pathway leading to chemoattractant-triggered actin assembly, integrin-dependent adhesion, and chemotaxis. Selective inhibitors of classical and novel protein kinase C isozymes do not prevent chemoattractant-induced neutrophil adhesion and chemotaxis. In contrast, chelerythrine chloride and synthetic myristoylated peptides with sequences based on the endogenous zeta protein kinase C pseudosubstrate region block agonist-induced adhesion to fibrinogen, chemotaxis and F-actin accumulation. Biochemical analysis shows that chemoattractants trigger rapid translocation of zeta protein kinase C to the plasma membrane accompanied by rapid but transient increase of the kinase activity. Moreover, pretreatment with C3 transferase, a specific inhibitor of Rho small GTPases, blocks zeta but not alpha protein kinase C plasma membrane translocation. Synthetic peptides from zeta protein kinase C also inhibit phorbol ester-induced integrin-dependent adhesion but not NADPH-oxidase activation, and C3 transferase pretreatment blocks phorbol ester-triggered translocation of zeta but not a! protein kinase C. These data suggest the involvement of zeta protein kinase C in chemoattractant-induced leukocyte integrin-dependent adhesion and chemotaxis. Moreover, they highlight a potential link between atypical protein kinase C isozymes and Rho signaling pathways leading to integrin-activation.