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
Date Published2007 Jun 22
KeywordsAnimals, Brain, Holoenzymes, Microfilament Proteins, Nerve Tissue Proteins, Phosphoprotein Phosphatases, Protein Phosphatase 1, Recombinant Proteins, Substrate Specificity, Swine

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.

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