title: cMyBP-C as a promiscuous substrate: phosphorylation by non-PKA kinases and its potential significance.
abstract: It is now generally accepted that phosphorylation of cMyBP-C is critically important in maintaining normal cardiac function. Although much of the work to date on phospho-regulation of cMyBP-C has focused on the role of protein kinase A (PKA, also known as cAMP-dependent protein kinase), recent evidence suggests that a number of non-PKA serine/threonine kinases, such as Ca(2+)/calmodulin-dependent protein kinase II, protein kinase C, protein kinase D and the 90-kDa ribosomal S6 kinase are also capable of targeting this key regulatory sarcomeric protein. This article reviews such evidence and proposes a hypothetical role for some of the pertinent signalling pathways in phospho-regulation of cMyBP-C in the setting of heart failure.
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: Sonya C
authors.initials: SC
authors.lastname: Bardswell
authors.forename: Friederike
authors.initials: F
authors.lastname: Cuello
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Kentish
authors.forename: Metin
authors.initials: M
authors.lastname: Avkiran
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009210:Myofibrils / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D000099163:Myosin Binding Protein C
chemical_list: D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D000099163:Myosin Binding Protein C; C089212:protein kinase D
references.citation: J Physiol. 2011 Mar 15;589(Pt 6):1367-82
references.pmid: 21242250
references.citation: J Mol Cell Cardiol. 1997 Jan;29(1):265-72
references.pmid: 9040041
references.citation: Circulation. 2009 Mar 10;119(9):1253-62
references.pmid: 19237661
references.citation: J Clin Invest. 2006 Apr;116(4):1005-15
references.pmid: 16585965
references.citation: J Mol Cell Cardiol. 2007 Aug;43(2):223-9
references.pmid: 17560599
references.citation: J Gen Physiol. 2010 Dec;136(6):615-27
references.pmid: 21115695
references.citation: J Mol Cell Cardiol. 2008 Aug;45(2):209-16
references.pmid: 18573260
references.citation: Circ Res. 2008 Feb 1;102(2):157-63
references.pmid: 18239146
references.citation: J Biol Chem. 1991 Feb 15;266(5):2811-7
references.pmid: 1671569
references.citation: J Biol Chem. 2010 Dec 31;285(53):41686-700
references.pmid: 21041300
references.citation: J Mol Cell Cardiol. 2011 Apr;50(4):613-20
references.pmid: 21291890
references.citation: Circ Res. 2008 Aug 1;103(3):244-51
references.pmid: 18599866
references.citation: Biochemistry. 2007 Jun 12;46(23):7054-61
references.pmid: 17503784
references.citation: J Physiol. 2000 Apr 1;524 Pt 1:205-19
references.pmid: 10747193
references.citation: J Mol Cell Cardiol. 2000 Jun;32(6):1013-23
references.pmid: 10888254
references.citation: Cardiovasc Res. 2002 Jan;53(1):131-7
references.pmid: 11744021
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16918-23
references.pmid: 17075052
references.citation: J Biol Chem. 1982 Jan 10;257(1):260-3
references.pmid: 7053370
references.citation: Acta Physiol Scand. 2003 Apr;177(4):449-58
references.pmid: 12648162
references.citation: J Proteome Res. 2010 Apr 5;9(4):1843-53
references.pmid: 20151718
references.citation: Basic Res Cardiol. 2010 Mar;105(2):289-300
references.pmid: 19655190
references.citation: Biophys J. 2001 Aug;81(2):1083-92
references.pmid: 11463649
references.citation: J Biol Chem. 2011 Feb 18;286(7):5300-10
references.pmid: 21148481
references.citation: J Mol Cell Cardiol. 2010 May;48(5):866-75
references.pmid: 19962384
references.citation: Circ Res. 2008 Mar 28;102(6):695-702
references.pmid: 18218981
references.citation: J Mol Cell Cardiol. 2001 Sep;33(9):1637-48
references.pmid: 11549343
references.citation: Circ Res. 2001 Dec 7;89(12):1184-90
references.pmid: 11739284
references.citation: Circulation. 2005 Feb 22;111(7):906-12
references.pmid: 15699252
references.citation: J Muscle Res Cell Motil. 2011 Nov;32(3):221-33
references.pmid: 21959857
references.citation: Heart Fail Rev. 2009 Dec;14(4):225-41
references.pmid: 19110970
references.citation: Cell Signal. 2005 May;17(5):655-64
references.pmid: 15683740
references.citation: Circ Res. 2004 May 28;94(10):1279-89
references.pmid: 15166115
references.citation: Cardiovasc Res. 2005 Apr 1;66(1):12-21
references.pmid: 15769444
references.citation: Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1220-8
references.pmid: 12763745
references.citation: Circ Res. 2005 Nov 25;97(11):1156-63
references.pmid: 16224063
references.citation: J Mol Cell Cardiol. 2012 Jan;52(1):154-64
references.pmid: 21971072
references.citation: Mol Cell Proteomics. 2009 Dec;8(12):2687-99
references.pmid: 19721077
references.citation: Circ Heart Fail. 2009 Nov;2(6):654-63
references.pmid: 19919991
references.citation: J Pharmacol Exp Ther. 1988 Dec;247(3):1039-45
references.pmid: 2849656
references.citation: Circ Res. 2011 Jul 8;109(2):141-50
references.pmid: 21597010
references.citation: EMBO J. 1995 May 1;14(9):1952-60
references.pmid: 7744002
references.citation: Circ Res. 2000 Feb 4;86(2):214-20
references.pmid: 10666418
references.citation: Clin Transl Sci. 2009 Oct;2(5):325-32
references.pmid: 20443916
references.citation: J Biol Chem. 2011 Mar 25;286(12):9913-9
references.pmid: 21257752
references.citation: J Mol Cell Cardiol. 2007 Dec;43(6):686-95
references.pmid: 17964599
references.citation: J Mol Cell Cardiol. 2010 Feb;48(2):322-30
references.pmid: 19883653
references.citation: Circ Res. 2007 Aug 31;101(5):503-11
references.pmid: 17641226
references.citation: Circ Res. 2007 Mar 30;100(6):864-73
references.pmid: 17322173
references.citation: J Mol Cell Cardiol. 2010 Dec;49(6):1003-11
references.pmid: 20850451
references.citation: Circ Res. 1997 Aug;81(2):268-73
references.pmid: 9242188
references.citation: Circulation. 2006 May 30;113(21):2516-23
references.pmid: 16717153
references.citation: J Biol Chem. 2010 Feb 19;285(8):5674-82
references.pmid: 20018870
references.citation: J Pharmacol Exp Ther. 1997 Feb;280(2):721-9
references.pmid: 9023284
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):222-31
references.pmid: 10997724
references.citation: J Physiol. 2003 Nov 1;552(Pt 3):845-57
references.pmid: 12923217
references.citation: Basic Res Cardiol. 2011 Jan;106(1):51-63
references.pmid: 20725733
references.citation: Circ Res. 2008 Oct 24;103(9):974-82
references.pmid: 18802026
references.citation: J Biol Chem. 2005 Jun 24;280(25):24135-42
references.pmid: 15840586
references.citation: J Biol Chem. 1993 Feb 5;268(4):2705-11
references.pmid: 8381412
references.citation: Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E395-402
references.pmid: 19934406
references.citation: Proteomics. 2006 Jul;6(14):4176-86
references.pmid: 16791825
references.citation: J Mol Cell Cardiol. 2007 Jan;42(1):247-59
references.pmid: 17081561
references.citation: Curr Opin Pharmacol. 2008 Apr;8(2):133-40
references.pmid: 18222727
references.citation: Circ Res. 2004 Nov 26;95(11):1091-9
references.pmid: 15514163
references.citation: Cardiovasc Res. 2006 Feb 1;69(2):370-80
references.pmid: 16380103
references.citation: J Physiol. 2004 Aug 1;558(Pt 3):927-41
references.pmid: 15194741
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8999-9003
references.pmid: 8799143
references.citation: FEBS Lett. 1999 Jun 25;453(3):254-9
references.pmid: 10405155
references.citation: Mol Pharmacol. 2007 Mar;71(3):799-806
references.pmid: 17142297
references.citation: J Mol Cell Cardiol. 2011 Oct;51(4):518-28
references.pmid: 21118696