Abstract
ERK8 is the most recent addition for the MAPK family, and its mechanism of activation and function are not yet known, mainly due to the lack of any known physiological stimulator. In this report, we describe the preparation of reagents for the use of a novel method, the ligand interaction scan (LIScan), to study the function of this protein kinase. We generated a set of mutants of ERK8, and identified inhibited as well as stimulated forms. By specifically inhibiting or stimulating the mutants of ERK8, we show that the ERK8-induced inhibition of proliferation is altered. Moreover, we used the developed mutants to show for the first time that ERK8 translocates to the nucleus upon activation. The use of methods such as the ligand interaction scan may thus promote the analyses of the functions of uncharacterized proteins such as ERK8, and possibly help in controlling the activity of target proteins in various experimental systems and applications.
References
Aug 25, 1989·Nucleic Acids Research·A HemsleyD J Galas
Feb 24, 1994·Nature·F ZhangE J Goldsmith
Oct 16, 1999·The Journal of Biological Chemistry·H RubinfeldR Seger
Mar 5, 2002·The Journal of Biological Chemistry·Mark K AbeMarsha Rich Rosner
Apr 20, 2002·Science·Guido GaiettaMark H Ellisman
Dec 10, 2002·Science·G ManningS Sudarsanam
Aug 15, 2003·Molecular and Cellular Biology·Lorin M HenrichDeborah A Lannigan
Apr 13, 2004·Journal of Cell Science·Ziv RavivRony Seger
Sep 17, 2004·Nature·Gregory J Hannon, John J Rossi
May 3, 2005·Nature Cell Biology·Jeffrey P MacKeiganJohn Blenis
Jun 3, 2005·Nature Reviews. Genetics·Mario R Capecchi
Sep 20, 2005·Molecular Biotechnology·Hadara Rubinfeld, Rony Seger
Dec 13, 2005·The Biochemical Journal·Iva V KlevernicPhilip Cohen
Jan 13, 2006·Nature Chemical Biology·Stuart L Schreiber
Feb 18, 2006·The Journal of Biological Chemistry·Carlo IavaroneMario Chiariello
Apr 21, 2006·The Journal of Biological Chemistry·Matthew P SaelzlerMark K Abe
Aug 2, 2006·EMBO Reports·Satoko Nishimoto, Eisuke Nishida
Dec 13, 2006·Biochimica Et Biophysica Acta·Phillipe Coulombe, Sylvain Meloche
Apr 24, 2007·Nature Methods·Oran ErsterMordechai Liscovitch
May 15, 2007·Oncogene·M RamanM H Cobb
Sep 2, 2008·Molecular Cell·Dana ChuderlandRony Seger
Oct 3, 2008·The Journal of Biological Chemistry·Vered Levin-SalomonDavid Engelberg
Jan 27, 2009·FEBS Letters·Iva V KlevernicPhilip Cohen
May 2, 2009·Molecular and Cellular Endocrinology·Eldar ZehoraiRony Seger