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首页> 外文期刊>Cell cycle >A crucial role for the phosphorylation of STRAP at Ser(188) by MPK38 in STRAP-dependent cell death through ASK1, TGF-beta, p53, and PI3K/PDK1 signaling pathways
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A crucial role for the phosphorylation of STRAP at Ser(188) by MPK38 in STRAP-dependent cell death through ASK1, TGF-beta, p53, and PI3K/PDK1 signaling pathways

机译：MPK38在Ser（188）处STRAP磷酸化在通过ASK1，TGF-beta，p53和PI3K / PDK1信号通路进行STRAP依赖性细胞死亡中的关键作用

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Serine-threonine kinase receptor-associated protein (STRAP) is a TGF- receptor-interacting protein that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP phosphorylation plays an important role in determining the pro- or anti-apoptotic function of STRAP. Murine protein serine/threonine kinase 38 (MPK38) phosphorylates STRAP at Ser(188) via direct interaction. Complex formation between STRAP and MPK38 is mediated by Cys(152) and Cys(270) of STRAP and Cys(339) and Cys(377) of MPK38, suggesting the redox dependency of this interaction. MPK38-mediated STRAP Ser(188) phosphorylation contributes to the pro-apoptotic function of STRAP by modulating key steps in STRAP-dependent ASK1, TGF-, p53, and PI3K/PDK1 signaling pathways. Moreover, knockdown of endogenous MPK38 using an inducible MPK38 shRNA system and in vivo activation of MPK38 by treatment of HEK293 and STRAP-null MEF cells with 1-chloro-2,4-dinitrobenzene (DNCB), a specific inhibitor of Trx reductase, provide evidence that STRAP Ser(188) phosphorylation plays a key role in STRAP-dependent cell death. Adenoviral delivery of MPK38 in mice also demonstrates that STRAP Ser(188) phosphorylation in the liver is tightly associated with cell death and proliferation through ASK1, TGF-, p53, and PI3K/PDK1 pathways, resulting in apoptotic cell death.
机译：丝氨酸-苏氨酸激酶受体相关蛋白（STRAP）是一种TGF-受体相互作用蛋白，可响应各种压力而参与细胞增殖和细胞死亡的调节。在这里，我们证明STRAP磷酸化在确定STRAP的促凋亡或抗凋亡功能中起重要作用。鼠蛋白丝氨酸/苏氨酸激酶38（MPK38）通过直接相互作用使Ser（188）的STRAP磷酸化。 STRAP和MPK38之间的复合物形成是由STRAP的Cys（152）和Cys（270）以及MPK38的Cys（339）和Cys（377）介导的，表明这种相互作用的氧化还原依赖性。 MPK38介导的STRAP Ser（188）磷酸化通过调节STRAP依赖性ASK1，TGF-，p53和PI3K / PDK1信号传导途径中的关键步骤，有助于STRAP的促凋亡功能。此外，使用可诱导的MPK38 shRNA系统敲除内源性MPK38，并通过用1-氯-2,4-二硝基苯（DNCB）（一种特异的Trx还原酶抑制剂）处理HEK293和STRAP无效的MEF细胞来体内激活MPK38。证据表明STRAP Ser（188）磷酸化在STRAP依赖性细胞死亡中起关键作用。小鼠中MPK38的腺病毒传递也表明肝脏中的STRAP Ser（188）磷酸化与细胞死亡和通过ASK1，TGF-，p53和PI3K / PDK1途径的增殖密切相关，从而导致凋亡性细胞死亡。

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