The families of kinases removing the Ca2+ releasing second messenger Ins(1,4,5)P3.
The formation and degradation of the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] are of great metabolic importance, because of its role in the mediation of calcium release from intracellular stores. The concentration of Ins(1,4,5)P3 in the cell is regulated by three signaling enzymes: phospholipase C isoforms release Ins(1,4,5)P3 from the plasma membrane by hydrolysis of phosphatidyl inositol 4,5-bisphosphate, whereas inositol phosphate 5-phosphatases remove it by dephosphorylation and a group of inositol phosphate kinases eliminate it by further phosphorylation at its 3- or 6-hydroxy group. The latter group is formed by the three isoforms of Ins(1,4,5)P3 3-kinase (IP3K) and inositol phosphate multikinase. In this article the tissue specific gene expression, molecular structure, role in calcium oscillations, regulation by calcium calmodulin, by phosphorylation and by intracellular localization of the IP3K isoforms are discussed. Another important aspect is the evolution of diverse inositol phosphate metabolizing enzymes from a eukaryotic founder by different mechanisms of gene diversification. Finally the role of IPMK in calcium signaling will be elucidated in more detail.
Nalaskowski
Marcus M
MM
Institute of Biochemistry and Molecular Biology 1: Cellular Signal Transduction, Center for Experimental Medicine, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Mayr
Georg W
GW
D000818:Animals; D020134:Catalytic Domain; D004789:Enzyme Activation; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats; D015290:Second Messenger Systems
D015544:Inositol 1,4,5-Trisphosphate; D010770:Phosphotransferases