Department of Anesthesiology

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Differential regulation of protein phosphatase-1(I) by neurabin.

TitleDifferential regulation of protein phosphatase-1(I) by neurabin.
Publication TypeJournal Article
Year of Publication2007
AuthorsS Bullock A, Platholi J, Gjyrezi A, Heerdt PM, Tung HYLim, Hemmings HC
JournalBiochem Biophys Res Commun
Volume358
Issue1
Pagination140-4
Date Published2007 Jun 22
ISSN0006-291X
KeywordsAnimals, Brain, Holoenzymes, Microfilament Proteins, Nerve Tissue Proteins, Phosphoprotein Phosphatases, Protein Phosphatase 1, Recombinant Proteins, Substrate Specificity, Swine
Abstract

Neurabin is a brain-specific actin and protein phosphatase-1 (PP-1) binding protein that inhibits the purified catalytic subunit of protein phosphatase-1 (PP-1(C)). However, endogenous PP-1 exists primarily as multimeric complexes of PP-1(C) bound to various regulatory proteins that determine its activity, substrate specificity, subcellular localization and function. The major form of endogenous PP-1 in brain is protein phosphatase-1(I) (PP-1(I)), a Mg(2+)/ATP-dependent form of PP-1 that consists of PP-1(C), the inhibitor-2 regulatory subunit, an activating protein kinase and other unidentified proteins. We have identified four PP-1(I) holoenzyme fractions (PP-1(IA), PP-1(IB), PP-1(IC), and PP-1(ID)) in freshly harvested pig brain separable by poly-L-lysine chromatography. Purified recombinant neurabin (amino acid residues 1-485) inhibited PP-1(IB) (IC(50)=1.1 microM), PP-1(IC) (IC(50)=0.1 microM), and PP-1(ID) (IC(50)=0.2 microM), but activated PP-1(IA) by up to threefold (EC(50)=40 nM). The PP-1(IA) activation domain was localized to neurabin(1-210). Our results indicate a novel mechanism of PP-1 regulation by neurabin as both an inhibitor and an activator of distinct forms of PP-1(I) in brain.

DOI10.1016/j.bbrc.2007.04.076
Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID17467665
PubMed Central IDPMC1989152
Grant ListMH 40899 / MH / NIMH NIH HHS / United States
P01 MH040899 / MH / NIMH NIH HHS / United States
P01 MH040899-20 / MH / NIMH NIH HHS / United States
R01 NS056315 / NS / NINDS NIH HHS / United States