Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2

The Journal of Biological Chemistry
Thomas TimmE Mandelkow

Abstract

MARK/Par-1, a kinase family with diverse functions particularly in inducing cell polarity, can phosphorylate microtubule-associated proteins in their repeat domain and cause their detachment from microtubules, and thereby microtubule destabilization. Because of its role in abnormal phosphorylation of the Tau protein in Alzheimer disease, we searched for regulatory kinases. MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. Because GSK3beta can also phosphorylate Tau at sites outside the repeat domain, the activation of GSK3beta, and concomitant inactivation of MARK can shift the pattern of pathological phosphorylation of Tau protein in Alzheimer disease.

References

Feb 1, 1994·Protein Science : a Publication of the Protein Society· MadhusudanJ M Sowadski
Apr 16, 2002·Nature Cell Biology·Veit RiechmannAnne Ephrussi
Apr 17, 2002·The Journal of Cell Biology·Britta J EickholtPatrick Doherty
Nov 14, 2002·Molecular Biology of the Cell·Jacek BiernatEva-Maria Mandelkow
Nov 15, 2002·Developmental Cell·Richard BentonDaniel St Johnston
Dec 10, 2002·Science·G ManningS Sudarsanam
Mar 18, 2003·Cellular Signalling·Takuji Tanoue, Eisuke Nishida
Oct 1, 2003·The EMBO Journal·Thomas TimmEva-Maria Mandelkow
Feb 26, 2004·The Journal of Cell Biology·David CohenAnne Müsch
Apr 16, 2004·Current Biology : CB·Jonathan B HurovHelen Piwnica-Worms
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
Jun 3, 2004·Nature Reviews. Drug Discovery·Philip Cohen, Michel Goedert
Jun 10, 2004·Current Biology : CB·James Spicer, Alan Ashworth
Sep 29, 2004·Trends in Biochemical Sciences·Gerard Drewes
Dec 24, 2004·Biochimica Et Biophysica Acta·Lester I BinderRobert W Berry
Jan 18, 2005·Cell·Takeshi YoshimuraKozo Kaibuchi
Feb 12, 2005·Science·Masashi KishiJoshua R Sanes
Jul 15, 2005·Molecular Biology of the Cell·Dorthe MateniaEva-Maria Mandelkow
Nov 1, 2005·The Journal of Biological Chemistry·Shinichi KosugaMasaya Imoto
Dec 21, 2005·Current Opinion in Cell Biology·Edwin M Munro
Feb 14, 2006·Structure·Saravanan PanneerselvamEckhard Mandelkow
May 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Y M ChenZ G Luo
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Naoya TochioShigeyuki Yokoyama
Nov 15, 2006·Current Drug Targets·Leung Kim, Alan R Kimmel
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Edda Thies, Eva-Maria Mandelkow
May 12, 2007·Brain Pathology·Eckhard MandelkowEva-Maria Mandelkow

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Citations

Mar 9, 2013·Cell Biochemistry and Biophysics·Farha NazMd Imtaiyaz Hassan
Jul 22, 2010·Nature Reviews. Neuroscience·Eun-Mi Hur, Feng-Quan Zhou
Feb 28, 2009·Acta Physiologica·N J BrightD Carling
Jul 24, 2013·Annual Review of Cell and Developmental Biology·Sandrine Etienne-Manneville
Apr 30, 2009·Annual Review of Neuroscience·Anthony P Barnes, Franck Polleux
Mar 2, 2013·The Journal of Endocrinology·Elizabeth I TangC Yan Cheng
Jun 2, 2011·International Journal of Alzheimer's Disease·Calum Sutherland
Jul 22, 2011·International Journal of Alzheimer's Disease·Diane P Hanger, Wendy Noble
May 27, 2014·Frontiers in Molecular Neuroscience·Sandra TenreiroTiago F Outeiro
Sep 2, 2008·Biochemical and Biophysical Research Communications·Takeshi TerabayashiHiroaki Miki
Oct 13, 2016·Molecular BioSystems·Daniel Ian McSkimmingNatarajan Kannan
Mar 19, 2011·Developmental Neurobiology·Maya Shelly, Mu-Ming Poo
Aug 17, 2018·International Journal of Molecular Sciences·Patrizia LoPresti
Sep 25, 2018·Expert Opinion on Therapeutic Targets·Przemysław DudaAgnieszka Gizak
Jun 19, 2009·Cell Motility and the Cytoskeleton·Gerold Schmitt-UlmsEva-Maria Mandelkow
Apr 2, 2019·Frontiers in Neuroscience·Ole Kristian DrangeOle A Andreassen
Aug 21, 2018·Current Drug Targets·Jahangir Alam, Lalit Sharma
Dec 4, 2019·PloS One·Tim SonntagMarc Montminy
Jan 15, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A MarxE Mandelkow
Apr 10, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Petranka KrumovaVeerle Baekelandt
May 31, 2020·International Journal of Molecular Sciences·Maria Carmela AnnunziataFabio Cattaneo
May 11, 2011·Developmental Neurobiology·Guo-Ying Yang, Zhen-Ge Luo
Feb 6, 2017·BMC Bioinformatics·Daniel Ian McSkimmingNatarajan Kannan
Jun 22, 2017·Cellular and Molecular Life Sciences : CMLS·Narendran AnnaduraiViswanath Das
Nov 11, 2019·Journal of Neuroscience Research·Manas Ranjan Sahu, Amal Chandra Mondal
Oct 5, 2018·Journal of Proteome Research·Matthew J MulcahyEdward Hawrot
Jun 30, 2009·Trends in Biochemical Sciences·Dorthe Matenia, Eva-Maria Mandelkow

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