title: Two dephosphorylation pathways of inositol 1,4,5-trisphosphate in homogenates of the cellular slime mould Dictyostelium discoideum.
abstract: Dictyostelium discoideum homogenates contain phosphatase activity which rapidly dephosphorylates Ins(1,4,5)P3 (D-myo-inositol 1,4,5-trisphosphate) to Ins (myo-inositol). When assayed in Mg2+, Ins(1,4,5)P3 is dephosphorylated by the soluble Dictyostelium cell fraction to 20% Ins(1,4)P2 (D-myo-inositol 1,4-bisphosphate) and 80% Ins(4,5)P2 (D-myo-inositol 4,5-bisphosphate). In the particulate fraction Ins(1,4,5)P3 5-phosphatase is relatively more active than the Ins(1,4,5)P3 1-phosphatase. CaCl2 can replace MgCl2 only for the Ins(1,4,5)P3 5-phosphatase activity. Ins(1,4)P2 and Ins(4,5)P2 are both further dephosphorylated to Ins4P (D-myo-inositol 4-monophosphate), and ultimately to Ins. Li+ ions inhibit Ins(1,4,5)P3 1-phosphatase, Ins(1,4)P2 1-phosphatase, Ins4P phosphatase and L-Ins1P (L-myo-inositol 1-monophosphate) phosphatase activities; Ins(1,4,5)P3 1-phosphatase is 10-fold more sensitive to Li+ (half-maximal inhibition at about 0.25 mM) than are the other phosphatases (half-maximal inhibition at about 2.5 mM). Ins(1,4,5)P3 5-phosphatase activity is potently inhibited by 2,3-bisphosphoglycerate (half-maximal inhibition at 3 microM). Furthermore, 2,3-bisphosphoglycerate also inhibits dephosphorylation of Ins(4,5)P2. These characteristics point to a number of similarities between Dictyostelium phospho-inositol phosphatases and those from higher organisms. The presence of an hitherto undescribed Ins(1,4,5)P3 1-phosphatase, however, causes the formation of a different inositol bisphosphatase isomer [Ins(4,5)P2] from that found in higher organisms [Ins(1,4)P2]. The high sensitivity of some of these phosphatases for Li+ suggests that they may be the targets for Li+ during the alteration of cell pattern by Li+ in Dictyostelium.
authors.affiliation: Zoological Laboratory, University of Leiden, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Van Lookeren Campagne
authors.forename: C
authors.initials: C
authors.lastname: Erneux
authors.forename: R
authors.initials: R
authors.lastname: Van Eijk
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D019794:2,3-Diphosphoglycerate; D002458:Cell Fractionation; D002851:Chromatography, High Pressure Liquid; D004023:Dictyostelium / Q000378:metabolism*; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D013403:Sugar Phosphates / Q000378:metabolism*
chemical_list: D004163:Diphosphoglyceric Acids; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D019794:2,3-Diphosphoglycerate; C044259:inositol 1,4-bis(phosphate); D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C043422:myo-inositol 1,4,5-triphosphate phosphatase