What we have learnt about PIKE from the knockout mice.

Phosphoinositide 3-kinase enhancer (PIKE) is a group of GTPase that belongs to the centaurin superfamily. These proteins have been discovered for more than a decade but our understandings on their functions are still limited. Studies from our research group and others have revealed some of their functions in a cellular context but their roles in organ development or systemic homeostasis just begin to unveil. The generation of PIKE knockout mice thus provides the valuable model to delineate the physiological roles of PIKE. In addition to being a PI3K/Akt enhancer, phenotypic characterization of the PIKE knockout mice demonstrates that the proteins are involved in multiple signaling cascades including Janus kinase (JAK)/ Signal Transducer and Activator of Transcription (STAT), AMP-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) and insulin receptor (IR)/Akt. In this article, we will review the current findings from the PIKE knockout mice studies and will discuss how these in vivo observations lead to the identifications of novel signaling cascades regulated by PIKE.