Multiple Functions of Phosphoinositide-3 Kinase Enhancer (PIKE)

• Type of Material: Article
• Authors: Chi Chan, Emory University; Keqiang Ye, Emory University
• Language: English
• Date: 2010-04-13
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2010 Chi Bun Chan and Keqiang Ye
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1100/tsw.2010.64
• Title of Journal or Parent Work: Scientific World Journal
• ISSN: 2356-6140
• Volume: 10
• Start Page: 613
• End Page: 623
• Grant/Funding Information: This work is supported by grant from NIH RO1 (NS060608) to K.Ye
• Keywords: CELL-ADHESION; apoptosis; cancer; Akt; NUCLEOTIDE EXCHANGE FACTOR; PIKE; GROWTH CONE GUIDANCE; Multidisciplinary Sciences; PHOSPHATIDYLINOSITOL 3-KINASE; WIDE LINKAGE SCAN; HUMAN-MALIGNANT GLIOMAS; phosphoinositide 3-kinase; FOCAL ADHESION KINASE; PHOSPHOLIPASE C-GAMMA-1; neuron; Environmental Sciences & Ecology; METABOTROPIC GLUTAMATE RECEPTORS; Environmental Sciences; PROTEIN-KINASE; Life Sciences & Biomedicine; Science & Technology - Other Topics; Science & Technology
• Research Categories: Health Sciences, Pathology

Abstract

GTP-binding proteins are the molecular switches of numerous cellular functions, including migration, proliferation, and differentiation. In the past 10 years, we have characterized a novel class of GTPases called phosphoinositide-3 kinase enhancer (PIKE) that interacts with PI3K/Akt. In neurons, PIKE is involved in the protective mechanisms against neuroexcitotoxic insults by linking various receptors, such as mGluR1 and Unc5H2, to the PI3K cascade. Interestingly, the PIKE gene (CENTG1) is also amplified in a variety of human cancers and enhances Akt activity, leading to their resistance against apoptosis and invasion. It has also been demonstrated that PIKE is involved in endosome formation and nuclear protein accumulation. Thus, PIKE possesses multitudinous biological functions rather than solely acting as an apoptosis inhibitor. In this review, we will update our current knowledge of the role of PIKE in various cellular activities. Moreover, the functions of PIKE in peripheral tissues as revealed by the unique phenotypes in PIKE knock-out mice will be discussed as well.