Chan Chi Bun, Ye Keqiang
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
J Cell Mol Med. 2007 Jan-Feb;11(1):39-53. doi: 10.1111/j.1582-4934.2007.00014.x.
Phosphoinositide-3-kinase enhancers (PIKE) are GTP-binding proteins that posses anti-apoptotic functions. The PIKE family includes three members, PIKE-L, PIKE-S and PIKE-A, which are originated from a single gene (CENTG1) through alternative splicing or differential transcription initiation. Both PIKE-S and PIKE-L bind to phosphoinositide-3-kinase (PI3K) and enhance its activity. PIKE-A does not interplay with PI3K. Instead, it interacts with the downstream effector Akt and promotes its activity. These actions are mediated by their GTPase activity. Because both PI3K and Akt are important effectors in the growth factor-mediated signaling which triggers cellular growth and acts against apoptosis, PIKEs therefore serve as the molecular switch that their activation are crucial for growth factors to exert their physiological functions. In this review, the current understanding of different PIKE isoforms in growth factors-induced anti-apoptotic function will be discussed. Moreover, the role of PIKE in the survival and invasion activity of cancer cells will also be introduced.
磷酸肌醇-3-激酶增强子(PIKE)是具有抗凋亡功能的GTP结合蛋白。PIKE家族包括三个成员,即PIKE-L、PIKE-S和PIKE-A,它们通过可变剪接或差异转录起始源自单个基因(CENTG1)。PIKE-S和PIKE-L均与磷酸肌醇-3-激酶(PI3K)结合并增强其活性。PIKE-A不与PI3K相互作用。相反,它与下游效应器Akt相互作用并促进其活性。这些作用由它们的GTP酶活性介导。由于PI3K和Akt都是生长因子介导的信号传导中的重要效应器,该信号传导触发细胞生长并对抗细胞凋亡,因此PIKE作为分子开关,其激活对于生长因子发挥其生理功能至关重要。在本综述中,将讨论目前对不同PIKE异构体在生长因子诱导的抗凋亡功能中的理解。此外,还将介绍PIKE在癌细胞存活和侵袭活性中的作用。