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Protein Kinase F A /GSK‐3 Phosphorylates on Ser 235 ‐Pro and Ser 404 ‐Pro that Are Abnormally Phosphorylated in Alzheimer's Disease Brain
Author(s) -
Yang ShiawDer,
Song JenShin,
Yu JauSong,
Shiah ShineGwo
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb09811.x
Subject(s) - phosphorylation , gsk 3 , kinase , tau protein , microbiology and biotechnology , gene isoform , biology , biochemistry , chemistry , alzheimer's disease , gene , medicine , pathology , disease
— Previously, we identified protein kinase F A /gly‐cogen synthase kinase‐3 (GSK‐3) as a microtubule‐associated protein kinase that can incorporate 4 mol of phosphates into 1 mol of protein and cause its electrophoretic mobility shift in sodium dodecyl sulfate gels, a unique property characteristic of paired helical filament‐associated pathological (PHF‐) in Alzheimer's disease brains. In this report, we identified TPPKS(p)PSAAK and SPVVSGDTS(p)PR as two phosphorylation site sequences phosphorylated by kinase F A /GSK‐3 in using peptide sequence analysis and sequential manual Edman degradation for radiosequencing. When mapping with human brain sequence, we further identified Ser 235 ‐Pro and Ser 404 ‐Pro as the two major phosphorylation sites according to the numbering of the longest isoform. Ser 235 and Ser 404 have been reported as two of the major abnormal phosphorylation sites in PHF‐. Taken together, the results provide initial evidence that protein kinase F A /GSK‐3 may represent one of the Ser‐Pro motif‐directed kinases involved in the abnormal phosphorylation of pathological PHF‐ in Alzheimer's disease brain.