Molecular study and regulation of D-myo-inositol 1,4,5-trisphosphate 3-kinase.
D-myo-Inositol 1,4,5-trisphosphate (InsP3) is a critical second messenger involved in signal transduction, i.e., calcium homeostasis. InsP3-kinase directly regulates the levels of InsP3 and D-myo-inositol 1,3,4,5-tetrakisphosphate (InsP4). InsP3 3-kinase is a calmodulin (CaM)-dependent enzyme and is also a target for phosphorylation by protein kinase C (PKC). Molecular cloning of cDNA's encoding proteins presenting InsP3 3-kinase activity establish the existence of distinct isoenzymes (at least three: A, B and C). These isoforms are differentially expressed and regulated by calcium/CaM. Site-directed mutagenesis and chemical modification of InsP3 3-kinase A led to the identification of three charged residues involved in ATP/Mg2+ binding among the catalytic domain and a hydrophobic residue taking part of the CaM binding site.
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Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire (IRIBHN), Université Libre de Bruxelles, Belgium.
Vanweyenberg
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Erneux
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D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology
D002147:Calmodulin; D007295:Inositol Phosphates; D007527:Isoenzymes; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D011493:Protein Kinase C; D002118:Calcium