Abstract
cGMP-dependent protein kinase-I (cGK-I) induces apoptosis in various cancer cell lines. However, the signaling mechanisms involved remain unknown. Using protein microarray technology, we identified a novel cGK substrate, death-associated protein kinase 2 (DAPK2), which is a Ca(2+)/calmodulin-regulated serine/threonine kinase. cGK-I phosphorylated DAPK2 at Ser(299), Ser(367) and Ser(368). Interestingly, a phospho-mimic mutant, DAPK2 S299D, significantly enhanced its kinase activity in the absence of Ca(2+)/calmodulin, while a S367D/S368D mutant did not. Overexpression of DAPK2 S299D also resulted in a twofold increase in apoptosis of human breast cancer MCF-7 cells as compared with wild-type DAPK2. These results suggest that DAPK2 is one of the targets of cGK-I in apoptosis induction.
References
Jan 1, 1995·Genes & Development·L P DeissA Kimchi
Aug 1, 1997·Trends in Biochemical Sciences·S M LohmannH R De Jonge
Mar 6, 1998·Molecular and Cellular Biology·T KawaiS Akira
Feb 27, 1999·Experimental Cell Research·T ShimojoF Marumo
Jun 22, 1999·Oncogene·T KawaiS Akira
Jan 11, 2000·Molecular and Cellular Biology·B InbalA Kimchi
Mar 7, 2001·The EMBO Journal·G ShaniA Kimchi
Oct 2, 2001·The Journal of Biological Chemistry·G ShohatA Kimchi
May 1, 2002·The Journal of Cell Biology·Boaz InbalAdi Kimchi
Jun 3, 2004·Cancer Research·Atsuko DeguchiI Bernard Weinstein
Dec 22, 2004·The Journal of Biological Chemistry·Paul R GravesTimothy A J Haystead
Sep 6, 2005·Cellular Signalling·Yali HouDarren D Browning
Oct 11, 2005·Current Biology : CB·Rana AnjumJohn Blenis
Nov 1, 2005·Cancer Letters·Yali HouDarren Browning
Dec 5, 2006·Autophagy·Devrim Gozuacik, Adi Kimchi
Feb 9, 2008·Cancer·In-Kiu KwonDarren D Browning
Oct 30, 2008·The Journal of Biological Chemistry·Hongbing LiKirill V Rosen
Mar 30, 2010·Oncogene·I-K KwonD D Browning
Mar 16, 2011·Cellular Signalling·Keizo YuasaAkihiko Tsuji
Apr 19, 2011·Journal of Molecular Biology·Ashok K PatelPetri Kursula
Apr 21, 2011·Cancer Prevention Research·Heather N TinsleyGary A Piazza
Jul 23, 2011·The FEBS Journal·Faranak FallahianMahmoud Aghaei
Nov 19, 2011·Cell Biochemistry and Function·Faranak FallahianSiamak Salami
Citations
Nov 4, 2015·Biochemical and Biophysical Research Communications·Kinuka IsshikiKeizo Yuasa
Jun 7, 2015·Biochemical and Biophysical Research Communications·Keizo YuasaAkihiko Tsuji
Jun 10, 2015·The International Journal of Biochemistry & Cell Biology·Barbara Geering
Jun 28, 2014·Seminars in Cancer Biology·Perrin F Windham, Heather N Tinsley
May 3, 2016·Structure·Bertrand SimonMatthias Wilmanns
Oct 21, 2015·Molecular and Cellular Biology·Barbara GeeringMartin Fussenegger
Oct 21, 2015·Oncogenesis·N MiyoshiT Shioda
Jul 5, 2013·American Journal of Physiology. Renal Physiology·Hasiyeti MaimaitiyimingShuxia Wang
Aug 27, 2016·Oncotarget·Thomas J WilsonPedro R Lowenstein
May 3, 2018·Nature Communications·Ruth ShilohAdi Kimchi
Oct 6, 2018·International Journal of Molecular Sciences·Mohamed ElbadawyKazuaki Sasaki
Aug 21, 2021·Communications Biology·Matej HorvathTomas Obsil