Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Raymond KwanM Bishr Omary

Abstract

Mallory-Denk bodies (MDBs) are hepatocyte inclusions that are associated with poor liver disease prognosis. The intermediate filament protein keratin 8 (K8) and its cross-linking by transglutaminase-2 (TG2) are essential for MDB formation. K8 hyperphosphorylation occurs in association with liver injury and MDB formation, but the link between keratin phosphorylation and MDB formation is unknown. We used a mutational approach to identify K8 Q70 as a residue that is important for K8 cross-linking to itself and other liver proteins. K8 cross-linking is markedly enhanced on treating cells with a phosphatase inhibitor and decreases dramatically on K8 S74A or Q70N mutation in the presence of phosphatase inhibition. K8 Q70 cross-linking, in the context of synthetic peptides or intact proteins transfected into cells, is promoted by phosphorylation at K8 S74 or by an S74D substitution and is inhibited by S74A mutation. Transgenic mice that express K8 S74A or a K8 G62C liver disease variant that inhibits K8 S74 phosphorylation have a markedly reduced ability to form MDBs. Our findings support a model in which the stress-triggered phosphorylation of K8 S74 induces K8 cross-linking by TG2, leading to MDB formation. These findings may extend...Continue Reading

References

Nov 1, 1991·Journal of Hepatology·P J Scheuer
Dec 1, 1974·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G G GlennerJ D Termine
Sep 1, 1969·Proceedings of the Society for Experimental Biology and Medicine·L BonarM M Skinner
Nov 1, 1983·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J TazawaS W French
May 29, 1999·Gastroenterology·C A MatteoniA J McCullough
Jan 10, 2002·The Journal of Biological Chemistry·Tao HeJohn E Eriksson
Jan 11, 2002·Experimental and Molecular Pathology·N E RileyS W French
Jun 12, 2002·Molecular Biology of the Cell·Diana M ToivolaM Bishr Omary
Oct 9, 2002·Current Medicinal Chemistry·R E Honkanen, T Golden
Jan 17, 2003·Journal of Neuropathology and Experimental Neurology·Gina M ZainelliNancy A Muma
Apr 23, 2003·Muscle & Nerve·Hans H Goebel
Nov 25, 2003·Digestive Diseases and Sciences·Helena Cortez-PintoMiguel Carneiro De Moura
Jan 14, 2005·Methods in Cell Biology·Nam-On KuM Bishr Omary
Dec 14, 2005·Experimental Cell Research·Guo-Zhong TaoM Bishr Omary
Dec 21, 2005·The Journal of Cell Biology·Ikuo NakamichiM Bishr Omary
May 26, 2006·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·R A Armstrong, N J Cairns
Jun 20, 2006·Trends in Biochemical Sciences·M Bishr OmaryJian Liao
Jul 5, 2006·The Journal of Cell Biology·Nam-On Ku, M Bishr Omary
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Masaru HaradaM Bishr Omary
May 29, 2007·Experimental Cell Research·Kurt ZatloukalM Bishr Omary
Dec 21, 2007·PLoS Biology·Daniel M PinkasChaitan Khosla
Mar 21, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dong-Myung ShinIn-Gyu Kim
May 6, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Masaru HaradaM Bishr Omary
Aug 13, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pavel StrnadM Bishr Omary
Sep 23, 2008·Biochimica Et Biophysica Acta·P StrnadH Denk
Oct 22, 2008·Journal of Hepatology·Vicência M R de LimaStephen H Caldwell
Jul 10, 2009·The Journal of Clinical Investigation·M Bishr OmaryShinichiro Hanada
Jul 10, 2009·The Journal of Clinical Investigation·Ronald K H Liem, Albee Messing
Jan 5, 2010·Trends in Cell Biology·D M ToivolaM B Omary

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Citations

Jan 30, 2013·The Journal of Cell Biology·Natasha T SniderM Bishr Omary
Jan 13, 2015·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Masaaki HiuraMasaru Harada
Feb 13, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ozlem KucukogluPavel Strnad
Jan 21, 2015·Current Opinion in Cell Biology·Diana M ToivolaPavel Strnad
Mar 16, 2017·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yuichi HonmaMasaru Harada
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Natasha T Snider, M Bishr Omary
Apr 1, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·M Bishr Omary
Jun 17, 2018·Biological Chemistry·Manuela D'ElettoMauro Piacentini
Jun 15, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kwi-Hoon JangNam-On Ku
Feb 4, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jared S ElenbaasM Bishr Omary
May 4, 2013·Journal of Cell Science·Amika SinglaM Bishr Omary

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