title: Rsk2 Knockdown in PC12 Cells Results in Sp1 Dependent Increased Expression of the Gria2 Gene, Encoding the AMPA Receptor Subunit GluR2.
abstract: The RSK2 protein is a member of the RSK serine-threonine protein kinase family and is encoded by the X-linked rps6ka3 gene in human. Highly heterogeneous  loss-of-function mutations affecting this gene are responsible for a severe syndromic form of cognitive impairment, Coffin-Lowry syndrome. RSK2, which is highly conserved in mammals, acts at the distal end of the Ras-ERK signaling pathway and is activated in response to growth factors and neurotransmitters. RSK2 is highly expressed in the hippocampus, and Rsk2-KO mice display spatial learning and memory impairment. We recently showed that ERK1/2 activity is abnormally increased in the hippocampus of  Rsk2-KO mice as well as the expression of the AMPA receptor subunit GluR2. The mechanism via which RSK2 deficiency affects the expression of GluR2 in neural cells was unknown. To address this issue we constitutively suppressed the expression of RSK2 in PC12 cells via vector-based shRNA in the present study. We show that Rsk2 silencing leads also to an elevation of ERK1/2 phosphorylation as well as of GluR2 expression and that the increased level of GluR2 expression results from the increased ERK1/2 activity on the transcription factor Sp1. Our results provide evidence that RSK2 modulates ERK1/2 activity on Sp1, which regulates GluR2 expression through transcriptional activation.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of Translational Medicine and Neurogenetics, INSERM U 964,  CNRS UMR 1704, Université de Strasbourg, 67404 Illkirch, France. tahiruosbiochem@yahoo.com.
authors: Tahir
authors: T
authors: Mehmood
authors: Anne
authors: A
authors: Schneider
authors: Solange
authors: S
authors: Pannetier
authors: André
authors: A
authors: Hanauer
references: J Physiol. 1995 Jul 15;486 ( Pt 2):305-12
references: 7473198
references: Neoplasia. 2007 May;9(5):406-17
references: 17534446
references: J Neurosci. 2006 Aug 9;26(32):8339-51
references: 16899729
references: Gene Expr Patterns. 2004 Jan;4(1):111-4
references: 14678837
references: J Neurosci. 1998 Sep 1;18(17):6723-39
references: 9712644
references: Science. 1991 May 10;252(5007):851-3
references: 1709304
references: Nat Rev Neurosci. 2004 Dec;5(12):952-62
references: 15550950
references: Neuroscience. 2009 Jan 12;158(1):105-25
references: 18424006
references: Cell Tissue Res. 2006 Nov;326(2):447-55
references: 16896950
references: J Neurochem. 2011 Nov;119(3):447-59
references: 21838783
references: Biochem Biophys Res Commun. 1999 Jan 19;254(2):454-61
references: 9918860
references: J Biol Chem. 2002 Jun 7;277(23):20631-9
references: 11904305
references: J Neurochem. 1996 Jan;66(1):1-5
references: 8522940
references: Mol Cell Endocrinol. 1999 May 25;151(1-2):65-77
references: 10411321
references: Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15006-11
references: 16217014
references: Mol Endocrinol. 2008 Jun;22(6):1449-63
references: 18372343
references: Neuron. 1995 Aug;15(2):453-62
references: 7646897
references: Eur J Neurosci. 2010 Jul;32(2):269-77
references: 20646058
references: Annu Rev Med. 2011;62:411-29
references: 21090964
references: Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424-8
references: 1065897
references: Hum Mol Genet. 2002 Nov 1;11(23):2929-40
references: 12393804
references: Pharmacol Rev. 1999 Mar;51(1):7-61
references: 10049997
references: Cell. 2004 Apr 30;117(3):387-98
references: 15109498
references: Biochim Biophys Acta. 2009 Oct;1793(10):1604-13
references: 19615412
references: Neuron. 2007 Jun 21;54(6):859-71
references: 17582328
references: Neuron. 1992 Jan;8(1):189-98
references: 1370372
references: J Med Genet. 2002 Oct;39(10):705-13
references: 12362025
references: J Neurosci. 1997 Dec 15;17(24):9393-406
references: 9390995
references: J Neurocytol. 2003 Jan;32(1):71-8
references: 14618102
references: Hum Genet. 2011 Mar;129(3):255-69
references: 21116650
references: J Neurosci. 1997 Jan 1;17(1):58-69
references: 8987736
references: Behav Genet. 2007 Jan;37(1):31-50
references: 17033934
references: Nature. 1996 Dec 12;384(6609):567-70
references: 8955270
references: J Biol Chem. 2001 Jul 13;276(28):25929-38
references: 11340067
references: J Neurochem. 2008 Dec;107(5):1325-34
references: 18823370