An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production - PubMed (original) (raw)

Fig. 1.

Complex inositol signaling pathways in mice. Two proposed pathways for IP synthesis in mammals require the activation of phospholipase C (PLC) and conversion of phosphatidylinositol 4,5-bisphosphate, PI(4,5)P2, to I(1,4,5)P3. Pathway I has been shown to exist in Saccharomyces cerevisiae, Arabidopsis, Drosophila melanogaster, and Rattus norvegicus in which I(1,4,5)P3 is converted by Ipk2 (wide black arrows) in two steps to I(1,3,4,5,6)P5 by means of I(1,4,5,6)P4 or I(1,3,4,5)P4 intermediates. Ipk2 also participates in several other reactions as shown. The 2-kinase activity of Ipk1 (wide white arrows) converts IP5 to IP6 and is capable of generating branches of I(1,2,4,5,6)P5 or I(1,2,3,4,6)P5. An inositol pyrophosphate synthase (crosshatched arrow) is able to generate inositol pyrophosphate PP-IP4 or PP-IP5 species. Pathway II is initiated by an IP3 3-kinase (gray arrow) that generates I(1,3,4,5)P4 as its sole product, which is then converted to I(1,3,4)P3 by an IP 5-phosphatase (thin arrow) and I(1,3,4,6)P4 by means of a I(1,3,4)P3 5/6 kinase (stippled arrows). Ipk2 then acts as a 5-kinase to convert I(1,3,4,6)P4 to IP5, which is a substrate for Ipk1. In both pathways, Ipk2 and Ipk1 function in sequential steps.