2003年1月31日 · Activation of the c-Jun N-terminal kinase (JNK) by proinflammatory cytokines inhibits insulin signaling, at least in part, by stimulating phosphorylation of rat/mouse insulin receptor substrate 1 (Irs1) at Ser (307) (Ser (312) in human IRS1). Here we show that JNK mediated feedback inhibition of the i …

Chronic low-grade inflammation and FFA induced by obesity can activate JNK to phosphorylate insulin receptor substrates (IRS) 1 and 2 at Ser/Thr residues 18 and dephosphorylate IRS-1 Tyr residues, 21 which not only prevents IRS from activating downstream PI3K also the interaction of IRS with its upstream insulin receptor (IR).

Serine 307 is a major site of JNK phosphorylation in IRS-1. Mutation of serine 307 to alanine eliminates phosphorylation of IRS-1 by JNK and abrogates the inhibitory effect of TNFα on insulin-stimulated tyrosine phosphorylation of IRS-1.

2016年8月10日 · Our results demonstrated that Aβ 1–42 oligomers significantly induced ERS and JNK activation. In addition, in response to Aβ 1–42 oligomers, IRS-1 phosphorylation at serines 307, 318 and 612 was increased. Further, an increase in Tau hyperphosphorylation at threonine 181 was observed following Aβ 1–42 oligomer treatment.

2000年3月24日 · Serine 307 is a major site of JNK phosphorylation in IRS-1. Mutation of serine 307 to alanine eliminates phosphorylation of IRS-1 by JNK and abrogates the inhibitory effect of TNFα on insulin-stimulated tyrosine phosphorylation of IRS-1.

2016年8月10日 · In peripheral insulin signaling impairment, ERS interferes with insulin signaling through c-Jun. N-terminal kinase (JNK)-dependent insulin receptor substance-1 (IRS-1) serine phosphorylation. We conducted this study to determine whether a similar mechanism contributes to insulin signaling impairment in AD pathogenesis.

2011年2月13日 · 有研究证实，FFA和各类炎症因子如TNF-α 诱导了JNK的激活，提高了IRS-1 上丝氨酸磷酸化水平，从而减弱了胰岛素靶组织如肝脏和脂肪中胰岛素信号通路

N末端激酶（JNK）依赖性胰岛素受体物质1（IRS-1）丝氨酸磷酸化。 我们进行了这项研究，以确定是否类似的机制有助于AD发病机制中的胰岛素信号传导障碍。

2000年3月24日 · TNFalpha promotes multipotential signal transduction cascades, including the activation of the Jun NH (2)-terminal kinase (JNK). Endogenous JNK associates with IRS-1 in Chinese hamster ovary cells.

胰岛素激活胰岛素受体 (IR) 酪氨酸激酶，后者能够聚集并磷酸化各种底物对接蛋白，例如胰岛素受体底物 (IRS) 蛋白家族。 酪氨酸磷酸化的 IRS 会暴露出结合位点，供众多信号转导伴侣结合。 这其中 PI3K 对胰岛素功能有重要作用，并主要通过激活 Akt/PKB 和 PKCζ 级联实现。 Akt 激活后可通过抑制 GSK-3 诱导糖原合成；通过 mTOR 和下游成分进行蛋白质合成；通过抑制多个促凋亡因子（Bad、FoxO 转录因子、GSK-3 和 MST1）促进细胞存活。 Akt 可磷酸化并直接抑制 …