title: An inositolphosphate-binding immunophilin, IPBP12.
abstract: A novel inositolphosphate-binding protein has been identified and shown to be an immunophilin. This protein, which was isolated from human erythrocyte membranes and from K562 (human erythroleukemia) cell membranes, has robust peptidylprolyl cis-trans isomerase activity that is strongly inhibited by nanomolar concentrations of FK506 or rapamycin, indicating a member of the FKBP (FK506-binding protein) class. However, unlike the cytosolic FKBP12, the isomerase activity of this membrane-associated immunophilin is strongly inhibited by nanomolar concentrations of inositol 1,4, 5-trisphosphate (IP(3)), inositol 1,3,4,5-tetrakisphosphate (IP(4)), and phosphatidylinositol 4- and 4,5-phosphates, which are suggested to be physiological ligands. The demonstration of a single 12-kD protein that binds both IP(4) or IP(3) and anti-FKBP12 provides strong support for the inositolphosphate-binding immunophilin having an apparent mass of 12 kD, and it is suggested that the protein might be called IPBP12 for 12-kD inositol phosphate binding protein. When an internal tryptic peptide derived from IPBP12 was sequenced, a sequence also present in human cytokeratin 10 was identified, suggesting a cytoskeletal localization for the immunophilin. While purifying IPBP12, it was found that it is immunoprecipitated with specific proteins that include a protein kinase and a phosphoprotein phosphatase. The latter is indicated to be phosphoprotein phosphatase 2A (PP-2A). It is suggested that immunophilins promote the assembly of multiprotein complexes that often include a protein kinase or a phosphoprotein phosphatase or both.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA. cunnineb@umdnj.edu
authors.forename: E B
authors.initials: EB
authors.lastname: Cunningham
mesh_terms: D000595:Amino Acid Sequence; D015672:Erythroid Precursor Cells / Q000737:chemistry; D006801:Humans; D020104:Immunophilins / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism* / Q000494:pharmacology; D020014:K562 Cells / Q000737:chemistry; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D015290:Second Messenger Systems; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
chemical_list: D007295:Inositol Phosphates; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C400088:IPBP12 protein, human; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus