I1PP2A

Figure: SDS-PAGE pattern of purified preparations of I1PP2A and I2PP2A/SET. The gels were stained with Coomassie Blue. The position of marker proteins is indicated.

Background: The PP2A inhibitor proteins, I1PP2A and I2PP2A, were discovered in the laboratory of GloboZymes founder Dr. Zahi Damuni while he was a tenured professor at The Pennsylvania State University College of Medicine. There has been progress since that time in numerous laboratories around the world demonstrating further the significance of these proteins in various diseases including cancer and Alzheimers, for example. I1PP2A is highly expressed in some cancers. Purified preparations of the protein inhibit all forms of protein phosphatase 2A (PP2A) tested to date in a substrate-selective manner. The purified preparations inhibit PP2A potently (k_i ~ 0.1 – 0.5 nM) with Myelin Basic Protein (MBP) and Histone H1 but not with Casein as substrate. In contrast, the preparations stimulate PP1 in the presence of Mn2+. I1PP2A undergoes phosphorylation on serines and tyrosines in cells. The functional significance of the serine phosphorylation is unclear. Tyrosine phsophorylation of I1PP2A occurs in response to the antiproliferative lectin Jacalin, and causes the dissociation of I1PP2A from PP2A and the activation of the phosphatase.

References:  Li M, Makkinje A, Damuni Z. (1996) Biochemistry 35, 6998-7002; Vaesen, M. et al (1994) Biol Chem Hoppe Seyler 375, 113-126; Malek, S. N. et al (1990) J Biol Chem 265, 13400-13409; Li, M., Damuni, Z. (1998) Methods Mol Biol  93, 59-66; Katayose, Y. et al (2000) J Biol Chem 275, 9209-9214; Yu L-G et al (2004) J Biol Chem 279, 41377-41383