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Inactivation of glycogen synthase kinase‐3 by protein kinase C δ: implications for regulation of τ phosphorylation
Author(s) -
Tsujio Ichiro,
Tanaka Toshihisa,
Kudo Takashi,
Nishikawa Takashi,
Shinozaki Kazuhiro,
Grundke-Iqbal Inge,
Iqbal Khalid,
Takeda Masatoshi
Publication year - 2000
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/s0014-5793(00)01234-5
Subject(s) - wortmannin , gsk 3 , hyperphosphorylation , protein kinase c , phosphorylation , glycogen synthase , chemistry , protein kinase b , phosphatidylinositol , kinase , microbiology and biotechnology , biology
The role of the phosphatidylinositol 3‐kinase (PI3K) pathway in the hyperphosphorylation of τ was investigated in SY5Y human neuroblastoma cells. Wortmannin, an inhibitor of PI3K, induced transient (after 1 h) activation of glycogen synthase kinase‐3 (GSK‐3), hyperphosphorylation of τ and dose‐dependent cytotoxicity. However, continuous inactivation of protein kinase (PK) B was observed from 1 to 24 h, suggesting the involvement of protein kinase(s) other than PKB in the phosphorylation and inactivation of GSK‐3 after 3 h. In cells treated with wortmannin, PKC δ fragments were observed, and the PKC activity increased after 3 h, whereas treatment of cells with z‐DEVD‐fmk, an inhibitor of caspase 3, also inhibited fragmentation of PKC δ and induced continuous activation of GSK‐3. It is suggested that fragmentation of PKC δ during the process of apoptosis results in the phosphorylation and inactivation of GSK‐3 and consequently inhibition of the phosphorylation of τ.