Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2778-2789
An Inositolphosphate-Binding Immunophilin, IPBP12
Earlene Brown Cunningham
From the Department of Biochemistry and Molecular Biology, UMDNJ-New
Jersey Medical School, Newark, NJ.
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 (IP3), inositol 1,3,4,5-tetrakisphosphate
(IP4), 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 IP4 or IP3
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.
