Protein kinase C θ and ε promote T-cell survival by a rsk-dependent phosphorylation and inactivation of BAD
Protein kinase C θ and ε promote T-cell survival by a rsk-dependent phosphorylation and inactivation of BAD
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DOI：
10.1074/jbc.m007732200
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发表时间：
2000-11-24
影响因子：
4.8
通讯作者：
Auberger, P
中科院分区：
文献类型：
--
作者：
Bertolotto, C;Maulon, L;Auberger, P
MAPK和蛋白激酶C(PKC)信号通路均促进细胞存活，保护细胞免于死亡。在这里，我们证明了12-O-十四酰佛波醇-13-乙酸酯(TPA)可以阻止Fas诱导的T淋巴细胞的凋亡。TPA的作用可被PKC抑制剂GF109203X和显性负的PKC theta特异性地消除，PKC是PKCα的一个元件，这表明新的和传统的PKC亚型介导佛波酯的作用。此外，TPA促进丝氨酸112位BAD的磷酸化，这一作用可被GF109203X消除，但不能被MEK抑制剂PD98059所消除。固有活性PKC的表达增加了丝氨酸112处BAD的磷酸化，但不增加丝氨酸136处的BAD的磷酸化。此外，过度表达催化失活的p90Rsk(RSK2-KN)可促进Fas介导的细胞死亡。最后，RSK2-KN取消了固有活性的PKC的保护作用，并完全阻断了BAD对丝氨酸112的磷酸化。因此，新的PKC theta和PKC是通过p90Rsk依赖的磷酸化和BAD失活从Fas介导的T淋巴细胞凋亡中拯救T淋巴细胞的一个元件。
Both MAPK and protein kinase C (PKC) signaling pathways promote cell survival and protect against cell death. Here, we show that 12-O-tetradecanoylphorbol-13-acetate (TPA) prevents Fas-induced apoptosis in T lymphocytes. The effect of TPA was specifically abolished by the PKC inhibitor GF109203X and by dominant negative PKC theta, PKC is an element of, and PKC alpha, suggesting that novel and conventional PKC isoforms mediate phorbol ester action. Moreover, TPA stimulated phosphorylation of BAD at serine 112, an effect abrogated by GF109203X but not by the MEK inhibitor PD98059. Expression of constitutively active PKC increased the phosphorylation of BAD at serine 112 but not at serine 136. Additionally, Fas-mediated cell death was enhanced by overexpression of a catalytically inactive form of p90Rsk (Rsk2-KN). Finally, Rsk2-KN abolished the protective effect of constitutively active PKC and totally blocked phosphorylation of BAD on serine 112. Thus, novel PKC theta and PKC is an element of rescue T lymphocytes from Fas-mediated apoptosis via a p90Rsk-dependent phosphorylation and inactivation of BAD.