Inositol polyphosphate multikinase signaling in the regulation of metabolism.
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.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Joo-Young
JY
Lee
Young-ran
YR
Kim
Jina
J
Park
Seyun
S
Kim
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000601:Amino Acids, Essential / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation; D001120:Arginine / Q000378:metabolism; D002149:Energy Intake; D004734:Energy Metabolism; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015003:Yeasts / Q000201:enzymology / Q000378:metabolism
D000601:Amino Acids, Essential; D005656:Fungal Proteins; D007295:Inositol Phosphates; D001120:Arginine; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases