title: Regulation of inositol 1,4,5-trisphosphate receptor type 1 function during oocyte maturation by MPM-2 phosphorylation.
abstract: Egg activation and further embryo development require a sperm-induced intracellular Ca(2+) signal at the time of fertilization. Prior to fertilization, the egg's Ca(2+) machinery is therefore optimized. To this end, during oocyte maturation, the sensitivity, i.e. the Ca(2+) releasing ability, of the inositol 1,4,5-trisphosphate receptor type 1 (IP(3)R1), which is responsible for most of this Ca(2+) release, markedly increases. In this study, the recently discovered specific Polo-like kinase (Plk) inhibitor BI2536 was used to investigate the role of Plk1 in this process. BI2536 inactivates Plk1 in oocytes at the early stages of maturation and significantly decreases IP(3)R1 phosphorylation at an MPM-2 epitope at this stage. Moreover, this decrease in Plk1-dependent MPM-2 phosphorylation significantly lowers IP(3)R1 sensitivity. Finally, using in vitro phosphorylation techniques we identified T(2656) as a major Plk1 site on IP(3)R1. We therefore propose that the initial increase in IP(3)R1 sensitivity during oocyte maturation is underpinned by IP(3)R1 phosphorylation at an MPM-2 epitope(s).
authors.affiliation: Laboratory of Molecular and Cellular Signalling, Department of Molecular Cell Biology, K.U. Leuven, Campus Gasthuisberg, O&N1 Bus 802, B-3000 Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanderheyden
authors.forename: Takuya
authors.initials: T
authors.lastname: Wakai
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
authors.forename: Humbert
authors.initials: H
authors.lastname: De Smedt
authors.forename: Jan B
authors.initials: JB
authors.lastname: Parys
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003198:Computer Simulation; D016384:Consensus Sequence; D000939:Epitopes / Q000378:metabolism; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D000911:Antibodies, Monoclonal; D002118:Calcium; D018797:Cell Cycle Proteins; D000939:Epitopes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1