A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
复制标题
DOI：
10.1042/bj20061881
复制
发表时间：
2007-04-01
影响因子：
4.1
通讯作者：
Lamb, Richard F.
中科院分区：
文献类型：
--
作者：
Findlay, Greg M.;Yan, Lijun;Lamb, Richard F.
mTOR（雷帕霉素的哺乳动物靶蛋白）信号通路是细胞生长的关键调节因子，并且由生长因子和营养物如氨基酸控制。虽然已经阐明了从生长因子受体到mTOR的信号传导途径，但营养素介导信号传导的途径的特征很差。通过筛选在果蝇mTOR信号通路中具有活性的蛋白激酶，我们鉴定了一个Ste 20家族成员（MAP 4K 3），该成员是最大S6 K（S6激酶）/4 E-BP 1 [eIF 4 E（真核起始因子4 E）结合蛋白1]磷酸化所需的，并调节细胞生长。重要的是，MAP 4K 3活性受氨基酸调节，但不受生长因子胰岛素调节，也不受mTORC 1抑制剂雷帕霉素调节。因此，我们的研究结果提出了一个模型，营养物质通过激活MAP 4K 3向mTORC 1发出信号。
The mTOR (mammalian target of rapamycin) signalling pathway is a key regulator of cell growth and is controlled by growth factors and nutrients such as amino acids. Although signalling pathways from growth factor receptors to mTOR have been elucidated, the pathways mediating signalling by nutrients are poorly characterized. Through a screen for protein kinases active in the mTOR signalling pathway in Drosophila we have identified a Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] phosphorylation and regulates cell growth. Importantly, MAP4K3 activity is regulated by amino acids, but not the growth factor insulin and is not regulated by the mTORC1 inhibitor rapamycin. Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3.