title: Syndecan-4 signaling at a glance.
abstract: Syndecan-4, a ubiquitous cell surface proteoglycan, mediates numerous cellular processes through signaling pathways that affect cellular proliferation, migration, mechanotransduction and endocytosis. These effects are achieved through syndecan-4 functioning as both a co-receptor for the fibroblast growth factor receptors (FGFR1-FGFR4) and its ability to independently activate signaling pathways upon ligand binding. As an FGFR co-receptor, syndecan-4 strengthens the duration and intensity of downstream signaling upon ligand binding; this is particularly evident with regard to mitogen-activated protein kinase (MAPK) signaling. In contrast, syndecan-4 also functions as an independent receptor for heparin-binding growth factors, such as fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGFs). These signaling cascades affect canonical signaling components, such as the mammalian target of rapamycin (mTOR), AKT1 and the Rho family of GTPases. In combination with the integrin family of proteins, syndecan-4 is also able to form physical connections between the extracellular matrix (ECM) and cytoskeletal signaling proteins, and it has a key role in regulation of integrin turnover. This unique versatility of the interactions of syndecan-4 is characterized in this Cell Science at a Glance article and illustrated in the accompanying poster.
authors: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
authors: Arye
authors: A
authors: Elfenbein
authors: Michael
authors: M
authors: Simons
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D004705:Endocytosis; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D053671:Syndecan-4 / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; C508304:SDC4 protein, human; D053671:Syndecan-4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D005346:Fibroblast Growth Factors; C546842:MTOR protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020741:rho GTP-Binding Proteins
references: J Cell Physiol. 2000 Sep;184(3):373-9
references: 10911369
references: J Cell Biol. 2009 Jul 13;186(1):75-83
references: 19581409
references: J Biol Chem. 1998 Oct 2;273(40):25548-51
references: 9748216
references: J Biol Chem. 1998 May 1;273(18):10914-8
references: 9556568
references: Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2078-82
references: 12543640
references: J Cell Physiol. 2005 Apr;203(1):166-76
references: 15389626
references: J Mol Biol. 2006 Jan 27;355(4):651-63
references: 16310216
references: Mol Biol Cell. 2001 Feb;12(2):339-50
references: 11179419
references: Biochemistry. 1999 Nov 30;38(48):15871-7
references: 10625452
references: J Theor Biol. 2005 Apr 21;233(4):483-99
references: 15748910
references: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22102-7
references: 20080785
references: J Biol Chem. 2001 Dec 14;276(50):47483-8
references: 11585825
references: J Biol Chem. 2000 Mar 31;275(13):9410-7
references: 10734086
references: J Biol Chem. 2002 Sep 6;277(36):32970-7
references: 12087088
references: Nat Cell Biol. 2000 Dec;2(12):E231-6
references: 11146675
references: J Biol Chem. 2002 May 31;277(22):19946-51
references: 11889131
references: J Biol Chem. 1998 Mar 27;273(13):7303-10
references: 9516424
references: Science. 1993 Mar 26;259(5103):1918-21
references: 8456318
references: Curr Opin Cell Biol. 2001 Oct;13(5):578-83
references: 11544026
references: J Cell Biol. 2003 Apr 14;161(1):155-67
references: 12695503
references: Mol Cell. 2008 Oct 10;32(1):140-9
references: 18851840
references: J Biol Chem. 2002 Apr 5;277(14):12270-4
references: 11805099
references: Cell Signal. 2013 Jan;25(1):101-5
references: 22975683
references: Dev Cell. 2011 Oct 18;21(4):681-93
references: 21982645
references: J Biol Chem. 2003 Feb 28;278(9):7617-23
references: 12493766
references: Biochemistry. 2000 Apr 4;39(13):3788-96
references: 10736179
references: Soft Matter. 2007 Jan 3;3(3):372-376
references: 19458789
references: J Biol Chem. 2010 Jul 23;285(30):23296-308
references: 20472934
references: J Biol Chem. 1997 May 2;272(18):11805-11
references: 9115237
references: Small GTPases. 2012 Apr-Jun;3(2):73-9
references: 22790193
references: J Biol Chem. 2003 Apr 18;278(16):13795-802
references: 12571249
references: Development. 2008 May;135(10):1771-80
references: 18403410
references: Circ Res. 2006 Jun 9;98(11):1398-404
references: 16675718
references: J Biol Chem. 2006 Oct 27;281(43):32156-63
references: 16936286
references: Nat Cell Biol. 2012 Jun 03;14(7):677-85
references: 22660413
references: J Cell Biol. 2006 Jul 31;174(3):323-7
references: 16880267
references: Dev Cell. 2010 Sep 14;19(3):426-39
references: 20833364
references: Dev Cell. 2005 Sep;9(3):377-88
references: 16139226
references: Dev Cell. 2006 Jun;10(6):783-95
references: 16740480
references: Sci Signal. 2012 May 08;5(223):ra36
references: 22569333
references: J Cell Biol. 2005 Aug 29;170(5):793-802
references: 16129786
references: J Biol Chem. 1992 Mar 25;267(9):6435-41
references: 1556147
references: Circ Res. 2005 Mar 18;96(5):488-500
references: 15774861
references: J Biol Chem. 1998 May 8;273(19):11563-9
references: 9565572
references: Circ Res. 2003 Nov 14;93(10):e136-42
references: 14563712
references: Mol Biol Cell. 2004 Dec;15(12):5670-7
references: 15483051
references: Nat Rev Cancer. 2002 Feb;2(2):91-100
references: 12635172
references: J Biol Chem. 1999 Aug 20;274(34):24417-24
references: 10446222
references: J Biol Chem. 1997 Jun 6;272(23):14713-20
references: 9169435
references: Cell. 2004 Jan 23;116(2):167-79
references: 14744429
references: Cell. 1991 Feb 22;64(4):841-8
references: 1847668
references: J Cell Sci. 2004 Jul 1;117(Pt 15):3189-99
references: 15226395
references: J Biol Chem. 2010 May 7;285(19):14247-58
references: 20154082
references: Immunology. 2013 Feb;138(2):173-82
references: 23113638
references: Dev Cell. 2013 Mar 11;24(5):472-85
references: 23453597
references: Biochem J. 2000 Nov 1;351 Pt 3:607-12
references: 11042114
references: Mol Cell. 2002 Jun;9(6):1215-25
references: 12086619
references: J Biol Chem. 2006 Sep 15;281(37):26884-92
references: 16807244
references: Curr Opin Cell Biol. 2009 Aug;21(4):575-81
references: 19442504
references: Int J Biochem Cell Biol. 2008;40(1):72-83
references: 17706452
references: Biochemistry. 1992 Sep 22;31(37):8876-83
references: 1390674
references: Dev Cell. 2010 May 18;18(5):713-24
references: 20434959
references: J Biol Chem. 2002 Jun 7;277(23):20367-71
references: 11916978
references: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20782-7
references: 18093920
references: EMBO J. 1999 Jul 15;18(14):3909-23
references: 10406796
references: J Cell Biol. 2007 May 7;177(3):527-38
references: 17485492
references: Mol Biol Cell. 2008 Aug;19(8):3390-403
references: 18480409
references: J Cell Biol. 2002 May 13;157(4):715-25
references: 12011116
references: Nature. 2003 Jul 24;424(6947):461-4
references: 12879077
references: Int J Biochem Cell Biol. 2007;39(3):505-28
references: 17097330
references: Mol Cell. 2000 Sep;6(3):743-50
references: 11030354