Ins(1,4,5)P3 metabolism and the family of IP3-3Kinases

The release of Ca2+ from intracellular stores is triggered by the second messenger inositol (1,4,5)-trisphosphate (Ins(1,4,5)P-3) The regulation of this process is critically important for cellular homeostasis. Ins(1,4,5)P-3 is rapidly metabolised, either to mositol (1,4)-bisphosphate (Ins(1,4)P-2) by inositol polyphosphate 5-phosphatases or to inositol (1,3,4,5)-tetrakisphosphate (Ins(1,3,4,5)P-4) by one of a family of inositol (1,4,5)P-3 3-kinases (IP3-3Ks). Three isoforms Of IP3-3K have now been identified in mammals; they have a conserved C-terminal catalytic domain, but divergent N-termini. This review discusses the metabolism of Ins(1,4,5)P-3, compares the IP3-3K isofornis and addresses potential mechanisms by which their activity might be regulated. (C) 2003 Elsevier Inc, All rights reserved.