Pervanadate-induced reverse translocation and tyrosine phosphorylation of phorbol ester-stimulated protein kinase C betaII are mediated by Src-family tyrosine kinases in porcine neutrophils.

Pervanadate-induced reverse translocation and tyrosine phosphorylation of phorbol ester-stimulated protein kinase C betaII are mediated by Src-family tyrosine kinases in porcine neutrophils.
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DOI:
10.1016/j.bbrc.2003.12.163
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发表时间:
2004-02
影响因子:
3.1
通讯作者:
Hideyuki Takahashi;Kin-ya Suzuki;H. Namiki
Hideyuki Takahashi;Kin-ya Suzuki;H. Namiki
中科院分区:
生物学4区
文献类型:
--
作者:
Hideyuki Takahashi;Kin-ya Suzuki;H. Namiki

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蛋白激酶C(PKC)在活化后从胞质溶胶易位到质膜。佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)是一种有效的PKC激活剂,已知其可诱导PKC不可逆地易位至质膜,而不是由生理刺激引起的可逆易位和随后的快速返回至胞质溶胶(反向易位)。然而,我们先前已经证明酪氨酸磷酸酶(PTK)抑制剂诱导PMA刺激的PKCβII在猪多形核白细胞(PMNs)中反向易位。在本研究中,我们发现过钒酸盐,一种有效的PTK抑制剂,也诱导PMA刺激的PKCβII在猪PMN中的酪氨酸磷酸化。此外,发现Src家族酪氨酸激酶(PTKs)的特异性抑制剂PP 2可抑制过钒酸盐诱导的PKC β II的反向易位和PMA刺激的PKCβII的酪氨酸磷酸化,表明这两种过钒酸盐诱导的反应由Src家族PTKs介导。我们的研究结果为PKC的亚细胞定位和酪氨酸磷酸化之间的关系提供了新的见解。
Protein kinase C (PKC), upon activation, translocates from the cytosol to the plasma membrane. Phorbol 12-myristate 13-acetate (PMA), a potent PKC activator, is known to induce irreversible translocation of PKC to the plasma membrane, in contrast to the reversible translocation resulting from physiological stimuli and subsequent rapid return to the cytosol (reverse translocation). However, we have previously shown that tyrosine phosphatase (PTPase) inhibitors induce reverse translocation of PMA-stimulated PKCβII in porcine polymorphonuclear leukocytes (PMNs). In the present study, we showed that pervanadate, a potent PTPase inhibitor, also induces tyrosine phosphorylation of PMA-stimulated PKCβII in porcine PMNs. Furthermore, PP2, a specific inhibitor of Src-family tyrosine kinases (PTKs), was found to inhibit both pervanadate-induced reverse translocation and tyrosine phosphorylation of PMA-stimulated PKCβII, suggesting that these two pervanadate-induced responses are mediated by Src-family PTKs. Our findings provide novel insight into the relationship between the subcellular localization and tyrosine phosphorylation of PKC.