Protein kinase A phosphorylation of tau-serine 214 reorganizes microtubules and disrupts the endothelial cell barrier.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Bing ZhuTroy Stevens

Abstract

Intracellular cAMP is compartmentalized to near membrane domains in endothelium, where it strengthens endothelial cell barrier function. Phosphodiesterase 4D4 (PDE4D4) interacts with the spectrin membrane skeleton and prevents cAMP from accessing microtubules. Expression of a dominant-negative PDE4D4 peptide enables cAMP to access microtubules, where it results in phosphorylation of the nonneuronal microtubule-associated protein tau at serine 214. Presently, we sought to determine whether PKA is responsible for tau-Ser214 phosphorylation and furthermore whether PKA phosphorylation of tau-Ser214 is sufficient to reorganize microtubules and induce endothelial cell gaps. In cells expressing the dominant-negative PDE4D4 peptide, forskolin activated transmembrane adenylyl cyclases, increased cAMP, and induced tau-Ser214 phosphorylation that was accompanied by microtubule reorganization. PKA catalytic and regulatory I subunits, but not the regulatory II subunit, coassociated with reorganized microtubules. To determine the functional consequence of tau-Ser214 phosphorylation, wild-type human tau40 and tau40 engineered to possess an alanine point mutation (S214A) were stably expressed in endothelium. In cells expressing the dominant-ne...Continue Reading

References

Apr 1, 1989·Journal of Cellular Physiology·T J StelznerR F O'Brien
Nov 1, 1982·Circulation Research·D M ShasbyM J Peach
Aug 16, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·A D VerinJ G Garcia
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Jun 26, 2002·The Journal of Cell Biology·Donna L CioffiTroy Stevens
Apr 23, 2003·American Journal of Respiratory Cell and Molecular Biology·Irina PetracheAlexander D Verin
May 30, 2003·The Journal of Biological Chemistry·Kiyotaka TokurakuSusumu Kotani
Jul 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Dulal PandaLeslie Wilson
Mar 9, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anna A BirukovaAlexander D Verin
Mar 17, 2004·Molecular Biology of the Cell·Janis M BunkerStuart C Feinstein
Mar 27, 2004·Physiological Reviews·Jesus AvilaFelix Hernandez
Apr 2, 2004·The Journal of Biological Chemistry·Lisa M SalvadorMary Hunzicker-Dunn
May 25, 2004·Journal of Cellular Biochemistry·Krisztina TarAlexander D Verin
Jul 2, 2004·Molecular and Cellular Biochemistry·David JayMaría de la Luz Ibarra
Jul 24, 2004·American Journal of Physiology. Heart and Circulatory Physiology·J WaschkeF E Curry
Nov 13, 2004·Journal of Cell Science·Gail V W Johnson, William H Stoothoff
Dec 4, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna A BirukovaAlexander D Verin
Aug 24, 2005·FEBS Letters·Matthijs R H KooistraJohannes L Bos
May 27, 2006·The Journal of Biological Chemistry·Cathrine Rein CarlsonJohn D Scott
Feb 24, 2007·Current Opinion in Cell Biology·Darren L Beene, John D Scott
Jul 7, 2007·Physiological Reviews·Debbie Willoughby, Dermot M F Cooper
Jan 8, 2008·American Journal of Physiology. Heart and Circulatory Physiology·R H AdamsonF E Curry
Apr 9, 2008·Histochemistry and Cell Biology·Y BaumerJ Waschke
Jul 19, 2008·European Journal of Cell Biology·Magdalena J LorenowiczPeter L Hordijk
Jan 2, 2009·American Journal of Physiology. Cell Physiology·Nicolas Schlegel, Jens Waschke
Apr 28, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nutan PrasainTroy Stevens
Dec 8, 2009·Microvascular Research·Anna A BirukovaKonstantin G Birukov

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Citations

Jan 1, 2014·The Journal of General Physiology·Marco ContiWito Richter
Jan 24, 2003·American Journal of Respiratory Cell and Molecular Biology·Kurt R Stenmark, Sarah A Gebb
Mar 17, 2015·Acta Neuropathologica Communications·Laura J BlairChad A Dickey
Jun 5, 2004·Trends in Cardiovascular Medicine·Shannon McCueB Lowell Langille
Feb 22, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sarah L Sayner
Jun 21, 2018·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Wissam H FaourNabil El Zein
Sep 20, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·K A MorrowT Stevens
Jan 28, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zeina HarhousNabil El Zein
Feb 25, 2020·Experimental Neurology·Eric E Abrahamson, Milos D Ikonomovic

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