title: The CCN family of proteins: structure-function relationships.
abstract: The CCN proteins are key signalling and regulatory molecules involved in many vital biological functions, including cell proliferation, angiogenesis, tumourigenesis and wound healing. How these proteins influence such a range of functions remains incompletely understood but is probably related to their discrete modular nature and a complex array of intra- and inter-molecular interactions with a variety of regulatory proteins and ligands. Although certain aspects of their biology can be attributed to the four individual modules that constitute the CCN proteins, recent results suggest that some of their biological functions require cooperation between modules. Indeed, the modular structure of CCN proteins provides important insight into their structure-function relationships.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Holbourn
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
authors.forename: Bernard
authors.initials: B
authors.lastname: Perbal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000737:chemistry* / Q000502:physiology*; D002455:Cell Division; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014945:Wound Healing
chemical_list: D055511:CCN Intercellular Signaling Proteins; D018969:Insulin-Like Growth Factor Binding Proteins
references.citation: Matrix Biol. 2002 Mar;21(2):115-28
references.pmid: 11852228
references.citation: Biochem Biophys Res Commun. 1992 Feb 14;182(3):1208-17
references.pmid: 1371676
references.citation: Exp Cell Res. 1999 Apr 10;248(1):44-57
references.pmid: 10094812
references.citation: J Cell Commun Signal. 2007 Sep;1(2):91-102
references.pmid: 18481200
references.citation: Biol Reprod. 1998 Oct;59(4):828-35
references.pmid: 9746732
references.citation: Dev Biol. 2001 Apr 15;232(2):372-87
references.pmid: 11401399
references.citation: J Cell Commun Signal. 2007 Jun;1(1):59-65
references.pmid: 18481210
references.citation: J Biol Chem. 2007 Jul 6;282(27):20002-14
references.pmid: 17483092
references.citation: Nat Struct Mol Biol. 2004 May;11(5):481-8
references.pmid: 15064755
references.citation: Lancet. 2004 Jan 3;363(9402):62-4
references.pmid: 14723997
references.citation: J Cell Biol. 1995 Aug;130(3):503-6
references.pmid: 7542656
references.citation: J Biol Chem. 1995 Mar 31;270(13):7304-10
references.pmid: 7706271
references.citation: Dev Dyn. 2000 Jun;218(2):280-99
references.pmid: 10842357
references.citation: J Mol Biol. 2000 Jun 2;299(2):499-520
references.pmid: 10860755
references.citation: J Biol Chem. 1992 Sep 25;267(27):19349-55
references.pmid: 1527055
references.citation: Dig Liver Dis. 2005 Apr;37(4):269-74
references.pmid: 15788211
references.citation: Cell Cycle. 2008 May 1;7(9):1254-61
references.pmid: 18418052
references.citation: Cell. 1993 May 7;73(3):421-4
references.pmid: 8490958
references.citation: Breast Cancer Res. 2005;7(6):R1080-9
references.pmid: 16457688
references.citation: Endocr Rev. 1999 Dec;20(6):761-87
references.pmid: 10605625
references.citation: Biochimie. 2006 Dec;88(12):1973-81
references.pmid: 16938382
references.citation: J Cell Biol. 2006 Nov 20;175(4):563-9
references.pmid: 17101694
references.citation: J Cell Biol. 1986 Nov;103(5):1635-48
references.pmid: 2430973
references.citation: Arteriosclerosis. 1989 Jan-Feb;9(1):21-32
references.pmid: 2463827
references.citation: Vitam Horm. 2005;70:69-103
references.pmid: 15727802
references.citation: Methods Enzymol. 1987;146:174-95
references.pmid: 2891018
references.citation: J Mol Biol. 2000 Sep 8;302(1):205-17
references.pmid: 10964570
references.citation: Genes Dev. 1996 Jul 1;10(13):1580-94
references.pmid: 8682290
references.citation: Nat Cell Biol. 2002 Aug;4(8):599-604
references.pmid: 12134160
references.citation: Annu Rev Cell Dev Biol. 2007;23:69-92
references.pmid: 17474876
references.citation: Dev Dyn. 2008 Feb;237(2):485-93
references.pmid: 18213577
references.citation: Curr Opin Genet Dev. 2003 Aug;13(4):365-71
references.pmid: 12888009
references.citation: J Cell Biol. 1993 Apr;121(2):469-77
references.pmid: 8468356
references.citation: J Biol Chem. 2004 Oct 15;279(42):44177-87
references.pmid: 15322081
references.citation: J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10
references.pmid: 17130294
references.citation: Development. 2000 Feb;127(4):821-30
references.pmid: 10648240
references.citation: Exp Cell Res. 2008 Mar 10;314(5):1094-104
references.pmid: 18201696
references.citation: Bone. 2006 May;38(5):671-7
references.pmid: 16311085
references.citation: FEBS Lett. 1993 Jul 26;327(2):125-30
references.pmid: 7687569
references.citation: J Biol Chem. 2003 Jun 27;278(26):24200-8
references.pmid: 12695522
references.citation: J Cell Biol. 2002 Oct 28;159(2):373-82
references.pmid: 12391027
references.citation: Mol Pathol. 2003 Apr;56(2):127-8
references.pmid: 12665631
references.citation: Biochem Biophys Res Commun. 2008 Apr 11;368(3):808-14
references.pmid: 18275847
references.citation: Endocr Rev. 2002 Dec;23(6):824-54
references.pmid: 12466191
references.citation: Int J Biochem Cell Biol. 2004 Jun;36(6):969-74
references.pmid: 15094110
references.citation: Angiogenesis. 2007;10(1):1-11
references.pmid: 17149534
references.citation: Proteins. 2008 Feb 15;70(3):611-25
references.pmid: 17876813
references.citation: FASEB J. 2005 May;19(7):729-38
references.pmid: 15857887
references.citation: Biochem Soc Trans. 2006 Jun;34(Pt 3):458-60
references.pmid: 16709187
references.citation: Curr Opin Genet Dev. 1996 Aug;6(4):432-8
references.pmid: 8791534
references.citation: J Biol Chem. 2003 Sep 5;278(36):33801-8
references.pmid: 12826661
references.citation: Mol Pathol. 2001 Apr;54(2):103-4
references.pmid: 11322165
references.citation: Curr Opin Struct Biol. 1995 Jun;5(3):391-5
references.pmid: 7583638
references.citation: J Biol Chem. 1997 Jul 18;272(29):18000-6
references.pmid: 9218427
references.citation: Cell Commun Signal. 2006 Feb 20;4:3
references.pmid: 16504021
references.citation: Front Biosci. 2005 May 01;10:998-1009
references.pmid: 15769600
references.citation: Exp Cell Res. 2007 Mar 10;313(5):952-64
references.pmid: 17239853
references.citation: Blood. 2006 Sep 1;108(5):1716-23
references.pmid: 16670264
references.citation: Cancer Cell Int. 2003 Aug 22;3(1):15
references.pmid: 12969515
references.citation: J Biol Chem. 2004 Dec 17;279(51):53857-66
references.pmid: 15466413
references.citation: Structure. 2005 Jan;13(1):155-67
references.pmid: 15642270
references.citation: Cytokine Growth Factor Rev. 1997 Sep;8(3):171-9
references.pmid: 9462483
references.citation: J Biol Chem. 1989 Nov 25;264(33):19514-27
references.pmid: 2584182
references.citation: Ann Surg Oncol. 2007 Jun;14(6):1909-18
references.pmid: 17406949
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):869-74
references.pmid: 9927660
references.citation: Endocr Rev. 1999 Apr;20(2):189-206
references.pmid: 10204117
references.citation: Science. 2001 Jul 6;293(5527):111-5
references.pmid: 11441185
references.citation: Oncogene. 2008 Apr 17;27(18):2552-60
references.pmid: 17968313
references.citation: EMBO J. 1998 Nov 16;17(22):6558-72
references.pmid: 9822601
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13028-33
references.pmid: 16924115
references.citation: J Cell Biochem. 2006 Sep 1;99(1):105-16
references.pmid: 16598765
references.citation: Mol Pathol. 2003 Apr;56(2):80-5
references.pmid: 12665625
references.citation: FASEB J. 2002 Feb;16(2):219-21
references.pmid: 11744618
references.citation: Biochemistry. 1996 Jul 2;35(26):8517-34
references.pmid: 8679613
references.citation: Mol Cell. 2003 Mar;11(3):605-17
references.pmid: 12667445
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12981-6
references.pmid: 9371786
references.citation: Adv Exp Med Biol. 2006;587:23-40
references.pmid: 17163153
references.citation: J Biol Chem. 2004 Oct 15;279(42):44166-76
references.pmid: 15308622
references.citation: Cancer Res. 2008 Feb 1;68(3):715-23
references.pmid: 18245471
references.citation: Cells Tissues Organs. 2007;185(1-3):95-9
references.pmid: 17587813
references.citation: Endocr Rev. 1995 Feb;16(1):3-34
references.pmid: 7758431
references.citation: PLoS One. 2007 Jun 20;2(6):e534
references.pmid: 17579708
references.citation: J Bone Miner Res. 2008 Nov;23(11):1751-64
references.pmid: 18597638
references.citation: J Cell Biol. 1991 Apr;113(1):195-205
references.pmid: 2007623
references.citation: J Endocrinol. 2003 Aug;178(2):169-75
references.pmid: 12904165
references.citation: J Biol Chem. 1993 Jul 25;268(21):15544-9
references.pmid: 8340381
references.citation: Biochem Biophys Res Commun. 2007 Mar 9;354(2):567-73
references.pmid: 17250806
references.citation: Nat Struct Biol. 2002 Mar;9(3):203-8
references.pmid: 11850637
references.citation: J Biol Chem. 2008 Apr 4;283(14):9239-47
references.pmid: 18276598
references.citation: J Cell Biochem. 2007 Aug 15;101(6):1475-91
references.pmid: 17340618
references.citation: Am J Pathol. 2002 Mar;160(3):849-59
references.pmid: 11891184
references.citation: J Cell Biol. 1999 Mar 8;144(5):1069-80
references.pmid: 10085302
references.citation: Virchows Arch. 2008 Jan;452(1):33-9
references.pmid: 18066593
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):701-9
references.pmid: 18245529
references.citation: J Mol Biol. 1993 May 20;231(2):445-58
references.pmid: 8510156
references.citation: J Biol Chem. 1997 Aug 8;272(32):20275-82
references.pmid: 9242708
references.citation: Expert Rev Mol Diagn. 2003 Sep;3(5):597-604
references.pmid: 14510180
references.citation: Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:893-900
references.pmid: 3151190
references.citation: J Biol Chem. 1990 Feb 15;265(5):2852-5
references.pmid: 2303431
references.citation: Endocrinology. 2006 Nov;147(11):5268-74
references.pmid: 16935848
references.citation: Proteins. 2006 Aug 15;64(3):665-72
references.pmid: 16736493
references.citation: Matrix Biol. 2000 Dec;19(7):597-614
references.pmid: 11102749
references.citation: Eur J Biochem. 2001 Dec;268(23):6058-65
references.pmid: 11732999
references.citation: J Biol Chem. 2002 Aug 16;277(33):29399-405
references.pmid: 12050162
references.citation: Mol Pathol. 2001 Apr;54(2):57-79
references.pmid: 11322167