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GSK3β Forms a Tetrameric Complex with Endogenous PS1‐CTF/NTF and β‐Catenin: Effects of the D257/D385A and FAD‐linked Mutations
Author(s) -
TESCO G.,
TANZI R. E.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06927.x
Subject(s) - endogeny , beta (programming language) , beta catenin , presenilin , immunoprecipitation , phosphorylation , chinese hamster ovary cell , catenin , microbiology and biotechnology , cell culture , biology , chemistry , signal transduction , biochemistry , genetics , medicine , wnt signaling pathway , disease , alzheimer's disease , computer science , programming language
A bstract : We have previously shown that the endogenous C‐terminal fragment of presenilin 1 coimmunoprecipitates with endogenous β‐catenin. Since PS1 has been suggested to be involved in β‐catenin stabilization, we further investigated whether GSK3β, responsible for β‐catenin phosphorylation and degradation, is part of the PS1/β‐catenin complex. In naïve H4 and CHO cells, PS1 co‐immunoprecipitated with both endogenous β‐catenin and GSK3β. In addition, GSK3β endogenously binds to the PS1‐CTF/NTF complex and β‐catenin in naïve CHO cells. GSK3β also co‐immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of γ‐secretase activity, we also tested whether PS1 endoproteolysis is required for β‐catenin/GSK3β/PS1 binding and whether PS1 FAD‐linked mutations affect GSK3β recruitment in the PS1/β‐catenin complex. GSK3β was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, ΔE10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and ΔE10) or the presence of PS1‐FAD mutations does not interfere with β‐catenin/GSK3β/PS1 complex formation.