par Erneux, Christophe ;Vanweyenberg, Valérie ;De Smedt, Florence ;Communi, David
Référence MS. Médecine sciences, 11, 2, page (240-246)
Publication Publié, 1995
Article révisé par les pairs
Résumé : Ins(1,4,5)P3 is a well-known inositol lipid-derived intracellular second messenger mobilizing intracellular calcium from internal stores. It is generated through two major signaling pathways: the former involves G proteins-coupled receptors and the latter tyrosine kinase-linked receptors. Ins(1,4,5)P3 mobilizes intracellular calcium by binding to its receptor, showing structural and physiological similarities with the ryanodine receptor (another intracellular calcium channel). It is metabolized by both an Ins(1,4,5)P3 5-phosphatase and 3-kinase reaction. Biochemical and molecular studies indicated at each step of the signal transduction pathway extensive molecular heterogeneity in the synthesis and degradation of inositol lipids derived molecules. Ins(1,4,5)P3 3-kinase consists in a family of calmodulin sensitive isoenzymes producing Ins(1,3,4,5)P4 (three isozymes). Ins(1,4,5)P3 5-phosphatase dephosphorylates both Ins(1,4,5)P3 and Ins(1,3,4,5)P4. It is interesting to note that the Lowe's oculocere-brorenal syndrome may be caused by a defect in a gene that encodes an enzyme that metabolizes Ins(1,4,5)P3, since type III of Ins(1,4,5)P3, 5-phosphatase shows high levels of sequence homology with the protein encoded by the Lowe's syndrome deficient gene. PtdIns(4,5)P2 is the phospholipase C substrate to generate Ins(1,4,5)P3 and diacylglycerol (DAG) but also the substrate of a specific 3-kinase to produce PtdIns(3,4,5)P3, another potential second messenger. Like phospholipase C, PtdIns(4,5)P2 3-kinase may be activated through G protein-coupled receptors or tyrosine kinase-linked receptors. The levels of Ins(3,4,5,6)P4 may also be regulated through the activation of receptors by extracellular signals and this molecule may also play a role of second messenger.

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