Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBPβ is required for hepatocyte proliferation induced by TGFα
Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBPβ is required for hepatocyte proliferation induced by TGFα
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DOI：
10.1016/s1097-2765(00)80237-3
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发表时间：
1999-12-01
期刊：
影响因子：
16
通讯作者：
Hunter, T
中科院分区：
文献类型：
--
作者：
Buck, M;Poli, V;Hunter, T
我们报告，TGF α诱导p90核糖体S激酶（RSK）的激活，这导致大鼠C/EBP β的Ser-105和小鼠C/EBP β的Thr-217的磷酸化，并伴随刺激分化的肝细胞增殖。此外，当野生型C/EBP β再表达时，C/EBP β（-/-）小鼠肝细胞对TGF α有反应，而当表达磷酸受体突变体大鼠C/EBP β Ala-105或小鼠C/EBP β Ala-217时，它们对TGF α的生长效应仍然不敏感。相反，表达磷酸化模拟突变体（大鼠C/EBP β Asp-105或小鼠C/EBP β Glu-217）的C/EBP β（-/-）肝细胞在不存在TGF α的情况下表现出显著的增殖。因此，转录因子C/EBP β的位点特异性磷酸化对于由TGF α和激活RSK的其他刺激物诱导的肝细胞增殖是至关重要的。
We report that TGF alpha induces activation of the p90 ribosomal S kinase (RSK), which results in the phosphorylation of rat C/EBP beta on Ser-105 and of mouse C/EBP beta on Thr-217 and concomitantly stimulates proliferation in differentiated hepatocytes. Moreover, C/EBP beta(-/-) mouse hepatocytes respond to TGF alpha when wild-type C/EBP beta is reexpressed, whereas they remain refractory to the growth effect of TGF alpha when expressing phosphoacceptor mutants rat C/EBP beta Ala-105 or mouse C/EBP beta Ala-217. In contrast, C/EBP beta(-/-) hepatocytes expressing the phosphorylation mimic mutants, rat C/EBP beta Asp-105 or mouse C/EBP beta Glu-217, exhibited marked proliferation in the absence of TGF alpha. Thus, a site-specific phosphorylation of the transcription factor C/EBP beta is critical for hepatocyte proliferation induced by TGF alpha and other stimuli that activate RSK.