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Dephosphorylation of microtubule‐associated protein tau by protein phosphatase‐1 and ‐2C and its implication in Alzheimer disease
Author(s) -
Gong Cheng-Xin,
Grundke-Iqbal Inge,
Damuni Zahi,
Iqbal Khalid
Publication year - 1994
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 - 10.1016/0014-5793(94)80247-5
Subject(s) - dephosphorylation , tau protein , protein phosphatase 2 , phosphatase , microtubule , phosphorylation , alzheimer's disease , chemistry , microbiology and biotechnology , disease , biochemistry , biology , medicine
Microtubule‐associated protein tau is abnormally hyperphosphorylated and forms the major protein subunit of paired helical filaments (PHF) in Alzheimer disease brains. The abnormally phosphorylated sites Ser‐199, Ser‐202, Ser‐396 and Ser‐404 but not Ser‐46 and Ser‐235 of Alzheimer tau were found to be dephosphorylated by protein phosphatase‐1 and this dephosphorylation was activated by Mn 2+ . In contrast, protein phosphatase‐2C did not dephosphorylate any of these sites. Both protein phosphatase‐1 and ‐2C had high activities towards [ 32 P]tau phosphorylated by cAMPdependent protein kinase. These results suggest that both protein phosphatase‐1 and ‐2C might be associated with normal phosphorylation state of tau, but only the former and not the latter phosphatase is involved in its abnormal phosphorylation in Alzheimer disease.