Isoform-specific contribution of protein kinase C to prion processing

Molecular and Cellular Neurosciences
Moustapha Alfa CisséBruno Vincent

Abstract

The cellular prion protein (PrP(c)) undergoes a physiological cleavage between amino acids 111 and 112, thereby leading to the secretion of an amino-terminal fragment referred to as N1. This proteolytic event is either constitutive or regulated by protein kinase C (PKC) and is operated by the disintegrins ADAM9/ADAM10 or ADAM17 respectively. We recently showed that the stimulation of the M1/M3 muscarinic receptors potentiates this cleavage via the phosphorylation and activation of ADAM17. We have examined the contribution of various PKC isoforms in the regulated processing of PrP(c). First we show that the PDBu- and carbachol-stimulated N1 secretions are blocked by the general PKC inhibitor GF109203X. We establish that HEK293 and human-derived rhabdhomyosarcoma cells over-expressing constitutively active PKCalpha, PKCdelta or PKCepsilon, but not PKCzeta, produce increased amounts of N1 and harbor enhanced ability to hydrolyze the fluorimetric substrate of ADAM17, JMV2770. Conversely, over-expression of the corresponding dominant negative proteins abolishes PDBU-stimulated N1 secretion and restores N1 to levels comparable to constitutive production. Moreover, deletion of PKCalpha lowers N1 recovery in primary cultured fibroblast...Continue Reading

References

Aug 11, 1995·The Journal of Biological Chemistry·S G ChenL Autilio-Gambetti
Jul 28, 1994·Nature·J CollingeJ G Jefferys
Jul 2, 1993·Cell·H BüelerC Weissmann
Apr 8, 1993·Nature·G ForloniF Tagliavini
Sep 26, 1997·FEBS Letters·P J MiddelhovenA J Verhoeven
Jun 26, 1998·The Biochemical Journal·H Mellor, P J Parker
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S B Prusiner
Dec 22, 1999·Biochemical and Biophysical Research Communications·S DemartJ P Deslys
Aug 23, 2000·The Journal of Biological Chemistry·B VincentF Checler
Sep 16, 2000·Science·S Mouillet-RichardO Kellermann
Sep 29, 2000·The Journal of Biological Chemistry·M EttaicheJ Chabry
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·D ViletteH Laude
Jan 28, 2004·Cell·Adriano Aguzzi, Magdalini Polymenidou
Jul 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·René EtcheberrigarayDaniel L Alkon
Sep 24, 2004·Trends in Pharmacological Sciences·Alastair W PooleMatthew L Jones
Oct 21, 2005·The Journal of Biological Chemistry·Moustapha Alfa CisséFrédéric Checler
Nov 3, 2005·FEBS Letters·Isabelle Laffont-ProustStéphane Haïk
Mar 2, 2006·Molecular and Cellular Biology·Alejandra CollazosDominique Joubert
Jun 30, 2006·Biochemical and Biophysical Research Communications·Moustapha Alfa CisséBruno Vincent
Apr 13, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Moustapha Alfa CisséFrédéric Checler

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Citations

Jan 31, 2013·The Journal of Biological Chemistry·Brian R FluhartyDavid A Harris
Oct 23, 2009·Molecular Biology of the Cell·Timothy J MyersSusan Wohler Sunnarborg
May 17, 2011·Molecular and Cellular Neurosciences·Moustapha CisseBruno Vincent
Jan 12, 2010·Archives of Biochemistry and Biophysics·Zhicheng WangKesheng Dai
Aug 15, 2013·Chembiochem : a European Journal of Chemical Biology·Yuzuru TaguchiGerald S Baron
Jun 14, 2019·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·Zengsheng ChenZhongjun J Wu
Apr 22, 2017·Frontiers in Molecular Biosciences·Andrew R Castle, Andrew C Gill

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