• Open Access

Inositol polyphosphate multikinase signaling in the regulation of metabolism


Seyun Kim, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea. seyunkim@kaist.ac.kr


Inositol phosphates (IPs) act as signaling messengers to regulate various cellular processes such as growth. Inositol polyphosphate multikinase (IPMK) generates inositol tetrakis- and pentakisphosphates (IP4 and IP5), acting as a key enzyme for inositol polyphosphate biosynthesis. IPMK was initially discovered as an essential subunit of the arginine-sensing transcription complex in budding yeast. In mammals, IPMK is also known as a physiologically important phosphatidylinositol 3 kinase (PI3K) that forms phosphatidylinositol 3,4,5-trisphosphate (PIP3), which activates Akt/PKB and stimulates its signaling. Acting in a catalytically independent fashion, IPMK mediates the activation of mammalian target of rapamycin (mTOR) in response to essential amino acids. In addition, IPMK binds and modulates AMP-activated protein kinase (AMPK) signaling pathways, including those involved in hypothalamic control of food intake. These recent findings strongly suggest that IPMK is a versatile player in insulin-, nutrient-, and energy-mediated metabolism signaling networks. Agents that control IPMK functions may provide novel therapeutics in metabolic syndromes such as obesity and diabetes.