Molecular Identification of I1PP2A, a Novel Potent Heat-Stable Inhibitor Protein of Protein Phosphatase 2A

• Published in: Biochemistry (Easton) 1996-06, Vol.35 (22), p.6998-7002
• Main Authors: LI, Mei, MAKKINJE, Anthony, DAMUNI, Zahi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Carrier Proteins; Cattle; DNA Primers - chemistry; Electrophoresis, Polyacrylamide Gel; Endoribonucleases; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Isopropyl Thiogalactoside - pharmacology; Molecular Sequence Data; Molecular Weight; Peptides - chemistry; Peptides - metabolism; Phosphoprotein Phosphatases - antagonists & inhibitors; Protein Phosphatase 1; Protein Phosphatase 2; Proteins - chemistry; Proteins - pharmacology; Recombinant Proteins - isolation & purification; Recombinant Proteins - pharmacology; RNA-Binding Proteins; Sequence Analysis; Trypsin - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi960581y

The amino acid sequences of two tryptic peptides derived from purified preparations of I1PP2A indicated that this potent heat-stable protein inhibitor of protein phosphatase 2A (PP2A) may be equivalent to putative histocompatibility leukocyte antigens class II-associated protein I (PHAP-I). Experiments using purified preparations of recombinant human PHAP-I confirmed that this protein inhibited PP2A. Half-maximal inhibition of the phosphatase occurred at about 4 nM PHAP-I, similar to the half-maximal inhibition obtained with purified preparations of bovine kidney I1PP2A. In addition, PHAP-I did not affect the activities of protein phosphatase 1, 2B, and 2C in a manner analogous to that of I1PP2A. Together, the results establish the identity of I1PP2A on a firm basis.