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Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice


Schild, A; Ittner, L M; Götz, J (2006). Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice. Biochemical and Biophysical Research Communications (BBRC), 343(4):1171-1178.

Abstract

Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes with diverse functions under physiologic and pathologic conditions such as Alzheimer's disease. All PP2A holoenzymes have in common a catalytic subunit C and a structural scaffolding subunit A. These core subunits assemble with various regulatory B subunits to form heterotrimers with distinct functions in the cell. Substrate specificity of PP2A in vitro is determined by regulatory subunits with leucine 309 of the catalytic subunit C playing a crucial role in the recruitment of regulatory subunits into the complex. Here we expressed a mutant form of Calpha, L309A, in brain and Harderian (lacrimal) gland of transgenic mice. We found an altered recruitment of regulatory subunits into the complex, demonstrating a role for the carboxyterminal leucine of Calpha in regulating holoenzyme assembly in vivo. This was associated with an increased phosphorylation of tau in brain and an impaired dephosphorylation of vimentin demonstrating that both cytoskeletal proteins are in vivo substrates of distinct PP2A holoenzyme complexes.

Abstract

Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes with diverse functions under physiologic and pathologic conditions such as Alzheimer's disease. All PP2A holoenzymes have in common a catalytic subunit C and a structural scaffolding subunit A. These core subunits assemble with various regulatory B subunits to form heterotrimers with distinct functions in the cell. Substrate specificity of PP2A in vitro is determined by regulatory subunits with leucine 309 of the catalytic subunit C playing a crucial role in the recruitment of regulatory subunits into the complex. Here we expressed a mutant form of Calpha, L309A, in brain and Harderian (lacrimal) gland of transgenic mice. We found an altered recruitment of regulatory subunits into the complex, demonstrating a role for the carboxyterminal leucine of Calpha in regulating holoenzyme assembly in vivo. This was associated with an increased phosphorylation of tau in brain and an impaired dephosphorylation of vimentin demonstrating that both cytoskeletal proteins are in vivo substrates of distinct PP2A holoenzyme complexes.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2006
Deposited On:18 Oct 2011 07:28
Last Modified:07 Dec 2017 09:10
Publisher:Elsevier
ISSN:0006-291X
Publisher DOI:https://doi.org/10.1016/j.bbrc.2006.03.066
PubMed ID:16580638

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