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首页> 外文期刊>Cell cycle >InAKTivation of insulin/IGF-1 signaling by dephosphorylation.
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InAKTivation of insulin/IGF-1 signaling by dephosphorylation.

机译：通过去磷酸化进行胰岛素/ IGF-1信号的InAKTivation。

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Signal transduction pathways are tightly regulated by phosphorylation-dephosphorylation cycles and yet the mammalian genome contains far more genes that encode for protein kinases than protein phosphatases. Therefore, to target specific substrates, many phosphatases associate with distinct regulatory subunits and thereby modulate multiple cellular processes. One such example is the C. elegans PP2A regulatory subunit PPTR-1 that negatively regulates the insulin/insulin-like growth factor signaling pathway to modulate longevity, dauer diapause, fat metabolism and stress resistance. PPTR-1, as well as its mammalian homolog B56beta, specifically target the PP2A enzyme to AKT and mediate the dephosphorylation of this important kinase at a conserved threonine residue. In C. elegans, the major consequence of this modulation is activation of the FOXO transcription factor homolog DAF-16, which in turn regulates transcription of its many target genes involved in longevity and stress resistance. Understanding the function of B56 subunits may have important consequences in diseases such as Type 2 diabetes and cancer where the balance of Akt phosphorylation is deregulated.
机译：信号转导途径受到磷酸化-去磷酸化周期的严格调控，但是哺乳动物基因组包含的编码蛋白激酶的基因远多于蛋白磷酸酶。因此，为了靶向特定的底物，许多磷酸酶与不同的调节亚基缔合，从而调节多个细胞过程。一个这样的例子是秀丽隐杆线虫PP2A调节亚基PPTR-1，其负调节胰岛素/胰岛素样生长因子信号传导途径以调节寿命，dauer滞育，脂肪代谢和抗逆性。 PPTR-1及其哺乳动物同系物B56beta专门将PP2A酶靶向AKT，并在保守的苏氨酸残基上介导该重要激酶的去磷酸化。在秀丽隐杆线虫中，这种调节的主要结果是激活了FOXO转录因子同源物DAF-16，后者又调节了涉及寿命和抗逆性的许多靶基因的转录。理解B56亚基的功能可能会对Akt磷酸化平衡失调的2型糖尿病和癌症等疾病产生重要影响。

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