NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling.
NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling.
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作者：
J. Romashkova;S. Makarov
细胞增殖和转化的机制与凋亡过程有内在联系：除非提供特定的存活信号，否则增殖细胞的默认状态是死亡。血小板源性生长因子（PDGF）是一种抑制细胞凋亡和促进细胞增殖的主要生存因子，但其介导抗细胞凋亡特性的机制尚未完全了解。在这里，我们表明，转录因子NF-κ B是重要的PDGF信号。NF-κ B传递两种信号：一种是诱导原癌基因c-myc和增殖所需的，第二种是抗凋亡信号，抵消c-Myc的细胞毒性。我们已经追踪了一个假定的途径，其中PDGF通过Ras和磷脂酰肌醇-3-激酶（PI（3）K）激活NF-κ B，再到PKB/Akt蛋白激酶和IkappaB激酶（IKK）; NF-κ B因此似乎是抗凋亡Ras/PI（3）K/Akt途径的靶点。我们发现，PDGF刺激后，Akt在体内瞬时与IKK结合并诱导IKK活化。这些发现确立了NF-κ B在生长因子信号传导中的作用，并定义了抗凋亡Ras/PI（3）K/Akt/IKK/NF-κ B途径，从而将抗凋亡信号传导与转录机制联系起来。
The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-kappaB is important in PDGF signalling. NF-kappaB transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates NF-kappaB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IkappaB kinase (IKK); NF-kappaB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kappaB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappaB pathway, thus linking anti-apoptotic signalling with transcription machinery.