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

Introduction The structure, tissue distribution and cellular localization of PIKEs Mitogenic PIKE‐S signaling in the nucleus Anti‐apoptotic function of PIKE‐L in neurons Role of PIKE‐L in merlin inhibited growth suppression Phosphoinositol lipids as a feedback regulator to PIKE‐L activation and translocation Anti‐apoptotic activity of PIKE‐A in cancers PIKE‐A as the physiological substrate of Fyn Perspective remarks AbstractPhosphoinositide‐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.