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Inhibitors of protein phosphatase‐2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau
Author(s) -
Tsujio Ichiro,
Zaidi Tanweer,
Xu Jiliu,
Kotula Leszek,
Grundke-Iqbal Inge,
Iqbal Khalid
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.097
Subject(s) - dephosphorylation , phosphatase , phosphorylation , chemistry , protein phosphatase 1 , protein phosphatase 2 , microbiology and biotechnology , neuroscience , biochemistry , biology
Protein phosphatase (PP)‐2A, which regulates the phosphorylation of tau, is regulated by two endogenous inhibitor proteins,I 1 PP 2 AandI 2 PP 2 A, in mammalian tissues. Here, we report the cloning ofI 1 PP 2 AandI 2 PP 2 Afrom human brain, and show that in PC12 cells and inI 1 PP 2 A ‐ GFP orI 2 PP 2 A ‐ GFP transfected NIH3T3 and human neural progenitor cells,I 1 PP 2 Ais localized mostly in the cell cytoplasm andI 2 PP 2 Amostly in the nucleus. The recombinantI 1 PP ‐ 2 AandI 2 PP ‐ 2 Ainhibit PP‐2A activity towards hyperphosphorylated tau in vitro; the dephosphorylation of the hyperphosphorylated tau at specific sites is selectively inhibited. Overexpression ofI 1 PP 2 Aas well asI 2 PP 2 Aresults in tau hyperphosphorylation and degeneration of PC 12 cells.