title: Cell signaling by protein carbonylation and decarbonylation.
abstract: Reactive oxygen species (ROS) serve as mediators of signal transduction. However, mechanisms of how ROS influence the target molecules to elicit signaling event have not been defined. Our laboratory recently accumulated evidence for the role of protein carbonylation in the mechanism of ROS signaling. This concept originated from experiments in which pulmonary artery smooth muscle cells were treated with endothelin-1 to understand the mechanism of cell growth. Endothelin-1 was found to promote protein carbonylation in an endothelin receptor- and Fenton reaction-dependent manner. Mass spectrometry identified proteins that are carbonylated in response to endothelin-1, including annexin A1. Our experiments generated a hypothesis that endothelin-1-mediated carbonylation and subsequent degradation of annexin A1 promote cell growth. This mechanism was found also to occur in response to other signaling activators such as serotonin and platelet-derived growth factor in smooth muscle cells of pulmonary circulation, systemic circulation, and the airway, as well as in cardiac muscle cells, suggesting the universal role of this pathway. We also discovered a process of decarbonylation that defines transient kinetics of carbonylation signals in certain conditions. We propose that protein carbonylation and decarbonylation serve as a mechanism of signal transduction.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Chi Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Lucia
authors.initials: L
authors.lastname: Marcocci
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.forename: Yuichiro J
authors.initials: YJ
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D050050:Protein Carbonylation / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D017305:Annexin A1; D019332:Endothelin-1; D017382:Reactive Oxygen Species
references.citation: J Biol Chem. 1969 Nov 25;244(22):6049-55
references.pmid: 5389100
references.citation: J Biol Chem. 1989 Feb 25;264(6):3341-6
references.pmid: 2563380
references.citation: J Biol Chem. 2003 May 9;278(19):17525-31
references.pmid: 12615926
references.citation: Lancet. 2003 May 3;361(9368):1533-44
references.pmid: 12737878
references.citation: Circulation. 2005 Nov 22;112(21):3297-305
references.pmid: 16286591
references.citation: Circulation. 2006 Apr 4;113(13):1708-14
references.pmid: 16585403
references.citation: Science. 1954 May 7;119(3097):623-6
references.pmid: 13156638
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1058-67
references.pmid: 11597896
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):813-24
references.pmid: 17848967
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L646-52
references.pmid: 11504692
references.citation: Revis Biol Celular. 1989;21:347-60
references.pmid: 2576881
references.citation: FASEB J. 1997 Jun;11(7):526-34
references.pmid: 9212076
references.citation: Proc Soc Exp Biol Med. 1992 Feb;199(2):165-70
references.pmid: 1741408
references.citation: EMBO J. 1991 Aug;10(8):2247-58
references.pmid: 2065663
references.citation: Nature. 1980 Sep 11;287(5778):147-9
references.pmid: 6893620
references.citation: Am J Physiol. 1999 Aug;277(2):L282-91
references.pmid: 10444522
references.citation: Mol Cell. 2007 Apr 13;26(1):1-14
references.pmid: 17434122
references.citation: Ann N Y Acad Sci. 2000;899:191-208
references.pmid: 10863540
references.citation: Curr Med Chem. 2001 Jun;8(7):763-72
references.pmid: 11375748
references.citation: Circulation. 2004 May 4;109(17):2150-5
references.pmid: 15078799
references.citation: Circ Res. 2005 Aug 5;97(3):227-35
references.pmid: 16002749
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943-7
references.pmid: 2263644
references.citation: Circ Res. 2000 Mar 17;86(5):494-501
references.pmid: 10720409
references.citation: Methods Mol Biol. 2000;99:15-24
references.pmid: 10909073
references.citation: J Biol Chem. 2003 Feb 14;278(7):4705-12
references.pmid: 12468531
references.citation: Circ Res. 1991 May;68(5):1362-8
references.pmid: 1850332
references.citation: FASEB J. 2005 Apr;19(6):641-3
references.pmid: 15703274
references.citation: Trends Pharmacol Sci. 2003 Sep;24(9):471-8
references.pmid: 12967772
references.citation: J Biol Chem. 1979 Apr 10;254(7):2214-20
references.pmid: 429281
references.citation: J Biol Chem. 1996 Sep 20;271(38):23317-21
references.pmid: 8798532
references.citation: Life Sci. 2000 Mar 24;66(18):PL265-70
references.pmid: 10809174
references.citation: Circ Res. 2004 Sep 17;95(6):579-86
references.pmid: 15297378
references.citation: Free Radic Biol Med. 2002 May 1;32(9):790-6
references.pmid: 11978480
references.citation: Cell. 2003 Dec 26;115(7):851-62
references.pmid: 14697203
references.citation: Free Radic Biol Med. 2008 Sep 15;45(6):847-54
references.pmid: 18616998
references.citation: Am J Physiol. 1992 Jan;262(1 Pt 2):H114-6
references.pmid: 1310231
references.citation: Circ Res. 1993 Nov;73(5):887-97
references.pmid: 8403258
references.citation: Am J Physiol. 1997 Mar;272(3 Pt 2):H1173-81
references.pmid: 9087590
references.citation: Am J Respir Cell Mol Biol. 2005 Jan;32(1):9-17
references.pmid: 15472139
references.citation: Am J Med. 1995 Sep;99(3):249-54
references.pmid: 7653484
references.citation: Methods Enzymol. 1994;233:346-57
references.pmid: 8015469
references.citation: Lancet. 2001 Oct 6;358(9288):1119-23
references.pmid: 11597664
references.citation: FEBS Lett. 2003 Jul 10;546(2-3):195-202
references.pmid: 12832039
references.citation: J Biol Chem. 2008 Aug 8;283(32):21837-41
references.pmid: 18445586
references.citation: Free Radic Biol Med. 2009 May 15;46(10):1411-9
references.pmid: 19268703
references.citation: Free Radic Biol Med. 1997;22(1-2):269-85
references.pmid: 8958153
references.citation: Free Radic Biol Med. 1996;20(2):215-23
references.pmid: 8746442
references.citation: Free Radic Biol Med. 1994 Nov;17(5):429-37
references.pmid: 7835749
references.citation: Br J Pharmacol. 2001 May;133(2):217-28
references.pmid: 11350857
references.citation: N Engl J Med. 2002 Mar 21;346(12):896-903
references.pmid: 11907289
references.citation: Exp Cell Res. 2003 Oct 15;290(1):93-107
references.pmid: 14516791
references.citation: Free Radic Biol Med. 1994 Jan;16(1):63-72
references.pmid: 8299998
references.citation: Am J Physiol. 1992 Dec;263(6 Pt 1):C1295-301
references.pmid: 1476170
references.citation: Neuroscience. 2005;132(2):313-24
references.pmid: 15802185
references.citation: Curr Top Cell Regul. 2000;36:1-30
references.pmid: 10842745
references.citation: Ann Intern Med. 1991 Mar 15;114(6):464-9
references.pmid: 1994793
references.citation: Nephron. 1996;74(1):39-44
references.pmid: 8883018
references.citation: Am J Respir Crit Care Med. 2002 Feb 1;165(3):398-405
references.pmid: 11818328
references.citation: Proc Natl Acad Sci U S A. 1974 Oct;71(10):4173-7
references.pmid: 4372610
references.citation: Science. 1995 Oct 13;270(5234):296-9
references.pmid: 7569979
references.citation: J Clin Invest. 2000 Jun;105(11):1555-62
references.pmid: 10841514
references.citation: Drug Metab Rev. 2006;38(4):651-75
references.pmid: 17145694
references.citation: Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):793-7
references.pmid: 1554204
references.citation: Proc Natl Acad Sci U S A. 1981 Apr;78(4):2120-4
references.pmid: 6113590
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8119-24
references.pmid: 17452640
references.citation: Circ Res. 2008 Feb 15;102(3):310-8
references.pmid: 18079412
references.citation: J Biol Chem. 2007 Feb 2;282(5):2918-28
references.pmid: 17142836
references.citation: Free Radic Biol Med. 1998 Mar 15;24(5):855-8
references.pmid: 9586816
references.citation: J Clin Invest. 2001 Oct;108(8):1141-50
references.pmid: 11602621
references.citation: Am J Physiol. 1996 Jan;270(1 Pt 1):L101-9
references.pmid: 8772532
references.citation: J Free Radic Biol Med. 1985;1(1):43-9
references.pmid: 3939136
references.citation: Antioxid Redox Signal. 2003 Dec;5(6):759-69
references.pmid: 14588149
references.citation: J Biol Chem. 1981 Mar 10;256(5):2427-32
references.pmid: 6257719
references.citation: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4884-8
references.pmid: 2112750
references.citation: Circ Res. 1994 Jun;74(6):1141-8
references.pmid: 8187280
references.citation: Circ Res. 1992 Mar;70(3):593-9
references.pmid: 1371430