PIKE GTPase are phosphoinositide-3-kinase enhancers, suppressing programmed cell death

Abstract

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.

1

Structure of PIKE proteins. Schematic representations of PIKE proteins (A) and partial alignment of the PH domains of rat PIKEs amino acids (B) were shown. The structure which is different from that of other isoforms in PIKE-A is shown in red. Identical amino acids were marked with an asterisk and the corresponding position of the amino acid in each protein was numbered.

2

A summary of PIKE signaling pathways.