Abstract
Mutations in PKD1 are the most common cause of autosomal dominant polycystic kidney disease (ADPKD). The protein product of PKD1 (polycystin-1 (PC1)) is a large transmembrane protein with a short intracellular C terminus that interacts with numerous signaling molecules, including Galpha(12). Cyst formation in ADPKD results from numerous cellular defects, including abnormal cilia, changes in polarity, and dysregulated apoptosis and proliferation. Recently, we reported increased apoptosis in Madin-Darby canine kidney (MDCK) cells through Galpha(12) stimulation of JNK and degradation of the anti-apoptotic protein Bcl-2 (Yanamadala, V., Negoro, H., Gunaratnam, L., Kong, T., and Denker, B. M. (2007) J. Biol. Chem. 282, 24352-24363). Herein, we confirm this pathway in Galpha(12)-silenced MDCK cells and utilize MDCK cell lines harboring either overexpressed or silenced PC1 to demonstrate that PC1 expression levels determine activity of the JNK/Bcl-2 apoptosis pathway. PC1-overexpressing MDCK cells were resistant to thrombin/Galpha(12)-stimulated apoptosis, JNK activation, and Bcl-2 degradation. In contrast, PC1-silenced MDCK cells displayed enhanced thrombin-induced apoptosis, JNK activity, and Bcl-2 degradation. In pulldown experimen...Continue Reading
References
Apr 25, 1995·Biochemistry·B M DenkerE J Neer
Jul 6, 1995·The New England Journal of Medicine·D Woo
Jan 1, 1994·Protein Science : a Publication of the Protein Society·E J Neer
Oct 22, 1993·Cell·D J VeisS J Korsmeyer
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·C J WardP C Harris
Oct 30, 1998·Biochemical and Biophysical Research Communications·S C ParnellJ P Calvet
Apr 13, 1999·Journal of Cellular Physiology·Y Ando-AkatsukaS Tsukita
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·E KimG Walz
Jun 11, 1999·The American Journal of Pathology·A C OngP C Harris
Dec 7, 2000·Molecular Cell·A BolettaG G Germino
Jan 12, 2002·The Journal of Biological Chemistry·Patrick DelmasJing Zhou
Mar 26, 2002·The Journal of Biological Chemistry·Stephen C ParnellJames P Calvet
Apr 27, 2002·The Journal of Biological Chemistry·Thomas E MeigsPatrick J Casey
May 23, 2002·The Journal of Biological Chemistry·Tobias N MeyerBradley M Denker
Mar 18, 2003·Molecular and Cellular Biology·Ying LuoJing Zhou
Aug 2, 2003·American Journal of Physiology. Cell Physiology·Tobias N MeyerBradley M Denker
Jun 19, 2004·Genomics·Takeshi YuasaJing Zhou
Mar 8, 2005·Trends in Pharmacological Sciences·Natalia A Riobo, David R Manning
Mar 12, 2005·The Journal of Clinical Investigation·Saori NishioToshio Mochizuki
Jan 10, 2006·Developmental Cell·Seng Hui LowThomas Weimbs
Feb 2, 2006·Molecular and Cellular Biology·Caroline ThiviergeMarie Trudel
Feb 3, 2006·Journal of the American Society of Nephrology : JASN·Manila BocaAlessandra Boletta
Feb 7, 2006·Current Medicinal Chemistry·Y LandryJ P Gies
Sep 29, 2006·Journal of the American Society of Nephrology : JASN·Lorenzo BattiniG Luca Gusella
May 17, 2007·Biochemistry·Patrick KellyThomas E Meigs
Jun 2, 2007·Biochemical and Biophysical Research Communications·Uma BasavannaMichael Sutters
Jun 15, 2007·The Journal of Biological Chemistry·Vijay YanamadalaBradley M Denker
Aug 3, 2007·Molecular Biology of the Cell·Manila BocaAlessandra Boletta
Feb 21, 2008·Journal of Cell Science·Ernesto SabathBradley M Denker
Apr 9, 2009·Journal of Cell Science·Andrew J StreetsAlbert C M Ong
Jul 4, 2009·Annual Review of Physiology·Jing Zhou
Jul 16, 2009·Current Molecular Medicine·Vijay YanamadalaBradley M Denker
Sep 25, 2009·Molecular Biology of the Cell·Tianqing KongBradley M Denker
Citations
Jun 6, 2012·PPAR Research·Daisuke YoshiharaShizuko Nagao
Aug 25, 2015·Frontiers in Physiology·Frank Park
Apr 15, 2015·Nature Reviews. Nephrology·Tamina Seeger-NukpezahErica A Golemis
Apr 29, 2010·Cell Adhesion & Migration·Tianqing KongBradley M Denker
Jun 14, 2012·Autophagy·Tobias B HuberZheng Dong
Jan 20, 2015·AIMS Molecular Science·Sarmed H KathemSurya M Nauli
Apr 8, 2017·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Steven Van LaeckeFrancis Verbeke
Feb 12, 2017·IUBMB Life·Liping SunXinzhou Zhang
Mar 14, 2018·Development·Bo ZhangOliver Wessely
Jan 13, 2018·Journal of Cellular Physiology·Lucia de StephanisGianluca Aguiari
May 20, 2015·Transplantation·Zhen WangChunyu Zeng
May 21, 2016·Physiological Genomics·Taketsugu Hama, Frank Park
Dec 11, 2014·Physiological Genomics·Jen X XuTianqing Kong
Jan 28, 2020·American Journal of Physiology. Renal Physiology·Elena Tutunea-FatanLakshman Gunaratnam
Sep 15, 2017·Scientific Reports·Yan TangXing-Zhen Chen
Aug 17, 2020·International Journal of Clinical Practice·Tung-Min YuChia-Hung Kao
Apr 20, 2020·Cellular Signalling·Robin L Maser, James P Calvet
Apr 27, 2020·Cellular Signalling·Caroline R SussmanVicente E Torres
Jun 12, 2017·Cell Calcium·Fernanda O Lemos, Barbara E Ehrlich
Apr 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Katrin MüllerTom Luedde
Jun 28, 2021·Gene·Runming WangYiming Xing
Dec 28, 2019·Cellular Signalling·Kristen L Nowak, Charles L Edelstein
Oct 31, 2021·Journal of the American Society of Nephrology : JASN·Xiaoqin ZhangXiaogang Li
Oct 12, 2010·Biochimica Et Biophysica Acta·Shakila Abdul-Majeed, Surya M Nauli