title: Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain.
abstract: Tenascin C (TNC) is an extracellular matrix protein that is upregulated during development as well as tissue remodeling. TNC is comprised of multiple independent folding domains, including 15 fibronectin type III-like (TNCIII) domains. The fifth TNCIII domain (TNCIII5) has previously been shown to bind heparin. Our group has shown that the heparin-binding fibronectin type III domains of fibronectin (FNIII), specifically FNIII12-14, possess affinity towards a large number of growth factors. Here, we show that TNCIII5 binds growth factors promiscuously and with high affinity. We produced recombinant fragments of TNC representing the first five TNCIII repeats (TNCIII1-5), as well as subdomains, including TNCIII5, to study interactions with various growth factors. Multiple growth factors of the platelet-derived growth factor (PDGF) family, the fibroblast growth factor (FGF) family, the transforming growth factor beta (TGF-β) superfamily, the insulin-like growth factor binding proteins (IGF-BPs), and neurotrophins were found to bind with high affinity to this region of TNC, specifically to TNCIII5. Surface plasmon resonance was performed to analyze the kinetics of binding of TNCIII1-5 with TGF-β1, PDGF-BB, NT-3, and FGF-2. The promiscuous yet high affinity of TNC for a wide array of growth factors, mediated mainly by TNCIII5, may play a role in multiple physiological and pathological processes involving TNC.
authors: Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Laura
authors: L
authors: De Laporte
authors: Jeffrey J
authors: JJ
authors: Rice
authors: Federico
authors: F
authors: Tortelli
authors: Jeffrey A
authors: JA
authors: Hubbell
mesh_terms: D000077214:Becaplermin; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D019063:Tenascin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020933:Neurotrophin 3; D010446:Peptide Fragments; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D019063:Tenascin; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin
references: Int J Biochem Cell Biol. 2004 Jun;36(6):986-90
references: 15094113
references: FASEB J. 2010 Dec;24(12):4711-21
references: 20671107
references: Adv Healthc Mater. 2013 Jan;2(1):57-71
references: 23184739
references: J Cell Sci. 2011 Apr 15;124(Pt 8):1288-300
references: 21429937
references: J Cell Physiol. 2011 Oct;226(10):2617-24
references: 21792920
references: Biochem Soc Trans. 2007 Aug;35(Pt 4):695-7
references: 17635125
references: Bioconjug Chem. 1999 Jan-Feb;10(1):75-81
references: 9893967
references: Sci Transl Med. 2011 Sep 14;3(100):100ra89
references: 21918106
references: Biochemistry. 2006 Aug 29;45(34):10319-28
references: 16922507
references: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21683-8
references: 19966216
references: Science. 2009 Nov 27;326(5957):1216-9
references: 19965464
references: Circ Res. 2006 Oct 13;99(8):853-60
references: 17008606
references: Genes Dev. 1992 Oct;6(10):1821-31
references: 1383086
references: J Cell Sci. 1999 Nov;112 ( Pt 22):3847-53
references: 10547346
references: Electrophoresis. 1993 Oct;14(10):1023-31
references: 8125050
references: J Biol Chem. 1991 Apr 25;266(12):7812-8
references: 2019604
references: Cardiovasc Res. 2011 Oct 1;92(1):19-28
references: 21712412
references: Circ Res. 2002 Jul 12;91(1):25-31
references: 12114318
references: J Pathol. 2003 Jul;200(4):488-99
references: 12845616
references: J Biol Chem. 1993 Feb 5;268(4):2542-53
references: 7679097
references: Dev Dyn. 2000 Jun;218(2):235-59
references: 10842355
references: J Biol Chem. 1989 Aug 5;264(22):13145-9
references: 2473987
references: J Cell Biochem. 2011 Nov;112(11):3354-63
references: 21751239
references: Crit Rev Immunol. 2011;31(2):115-45
references: 21542790
references: Int J Biochem Cell Biol. 2005 May;37(5):1066-83
references: 15743679
references: Virchows Arch. 2001 Aug;439(2):185-90
references: 11561759
references: Circ J. 2005 Apr;69(4):481-7
references: 15791047
references: Matrix Biol. 2001 Feb;20(1):13-22
references: 11246000
references: J Cell Biol. 1993 Mar;120(5):1079-81
references: 7679670
references: Biomaterials. 2003 Nov;24(24):4353-64
references: 12922148
references: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16002-7
references: 21911392
references: Biochem Biophys Res Commun. 2004 Sep 24;322(3):766-71
references: 15336530
references: Biomaterials. 2004 Aug;25(18):4513-20
references: 15046942
references: Cell Mol Life Sci. 2011 Oct;68(19):3175-99
references: 21818551
references: Adv Drug Deliv Rev. 2007 May 30;59(4-5):274-91
references: 17544542
references: J Biol Chem. 1995 Mar 3;270(9):4619-23
references: 7533163
references: Curr Opin Biotechnol. 1995 Oct;6(5):501-6
references: 7579661
references: Mol Vis. 2010 Jul 01;16:1194-205
references: 20664686
references: Nat Med. 2011 Jun 26;17(7):867-74
references: 21706029
references: Cancer Cell. 2011 Aug 16;20(2):139-41
references: 21840480