Ins (1,4,5)P3 derived from the plasma membrane phosphatidylinositol 4, 5-bisphosphate as a result of activation of a wide variety of cell surface receptors causes release of Ca´=´´ from nonmitochondrial, vesicular, intracellular stores by binding to a specific receptor. Termination of the Cat+-rnobilizing effect of Ins (1,4,5)P3 can occur by two distinct, mechanisms: Ins (1,4,5)P3 can be sequentially dephosphorylated to free inositol or it can be phosphorylated in an ATP-dependent process to Ins (1,3,4,5)P4. The roles of Ins (1,3,4,5)P4 include the modulation of intracellular Cat+ through either the re-uptake of Cat+ into intracellular stores or through control of the Cat+ transfer process between Ins (1,4,5)P3-sensitive and-insensitive pools. Ins (1,3,4,5)P4 is further metabolized to a consider-able number of inositol phosphate, including Ins (1,3,4,6)P4 and Ins (1,3,4,5,6)P5. Therefore, Ins (1,4,5)P3 3-kinase (IP3K), which catalyzes the phosphorylation of Ins (1,4,5)P3 to Ins (1,3,4,5)P4 not only occupies a central position in regulating the availability of two Cat-modulating second messengers but also provides an important branch point in the pathway of inositol phosphate metabolism. Accordingly, the activity of IP3K was regulated by a variety of cellular mechanisms; upon the concentration of Cat+ and calmodulin, C-AMP dependent protein kinase A, and DAG dependent protein kinase C etc.
In this article, the roles and biochemical properties of IP3K and the characteristics of its gene sequences were reviewed. In addition, the cross-talk mechanisms through the I113K between cellular signaling pathways which use various second messengers such as inositol phosphates, DAG, Cat+ and cAMP were also discussed.
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