Regulated Shedding of Syndecan-1 and -4 Ectodomains by Thrombin and Growth Factor Receptor Activation
Year: 1997
Type: article
Abstract: The syndecan family of transmembrane heparan sulfate proteoglycans is abundant on the surface of all adherent mammalian cells. Syndecans bind and modify the action of various growth factors/cytokines, proteases/antiproteases, cell adhesion molecules, and extracellular matrix components. Syndecan expression is highly regulated during wound repair, a process orchestrated by many of these effectors. Each syndecan ectodomain is shed constitutively by cultured cells, but the mechanism and significance of this shedding are not understood. Therefore, we examined (i) whether physiological agents active during wound repair influence syndecan shedding, and (ii) whether wound fluids contain shed syndecan ectodomains.Using SVEC4–10 endothelial cells we find that certain proteases and growth factors accelerate shedding of the syndecan-1 and -4 ectodomains. Protease-accelerated shedding is completely inhibited by serum-containing media. Thrombin activity is duplicated by the 14-amino acid thrombin receptor agonist peptide that directly activates the thrombin receptor and is not inhibited by serum. Epidermal growth factor family members accelerate shedding but FGF-2, platelet-derived growth factor-AB, transforming growth factor-β, tumor necrosis factor-α, and vascular endothelial cell growth factor 165 do not. Shed ectodomains are soluble, stable in the conditioned medium, have the same size core proteins regardless whether shed at a basal rate, or accelerated by thrombin or epidermal growth factor-family members and are found in acute human dermal wound fluids. Thus, shedding is accelerated by activation of at least two distinct receptor classes, G protein-coupled (thrombin) and protein tyrosine kinase (epidermal growth factor). Proteases and growth factors active during wound repair can accelerate syndecan shedding from cell surfaces. Regulated shedding of syndecans suggests physiological roles for the soluble proteoglycan ectodomains. The syndecan family of transmembrane heparan sulfate proteoglycans is abundant on the surface of all adherent mammalian cells. Syndecans bind and modify the action of various growth factors/cytokines, proteases/antiproteases, cell adhesion molecules, and extracellular matrix components. Syndecan expression is highly regulated during wound repair, a process orchestrated by many of these effectors. Each syndecan ectodomain is shed constitutively by cultured cells, but the mechanism and significance of this shedding are not understood. Therefore, we examined (i) whether physiological agents active during wound repair influence syndecan shedding, and (ii) whether wound fluids contain shed syndecan ectodomains. Using SVEC4–10 endothelial cells we find that certain proteases and growth factors accelerate shedding of the syndecan-1 and -4 ectodomains. Protease-accelerated shedding is completely inhibited by serum-containing media. Thrombin activity is duplicated by the 14-amino acid thrombin receptor agonist peptide that directly activates the thrombin receptor and is not inhibited by serum. Epidermal growth factor family members accelerate shedding but FGF-2, platelet-derived growth factor-AB, transforming growth factor-β, tumor necrosis factor-α, and vascular endothelial cell growth factor 165 do not. Shed ectodomains are soluble, stable in the conditioned medium, have the same size core proteins regardless whether shed at a basal rate, or accelerated by thrombin or epidermal growth factor-family members and are found in acute human dermal wound fluids. Thus, shedding is accelerated by activation of at least two distinct receptor classes, G protein-coupled (thrombin) and protein tyrosine kinase (epidermal growth factor). Proteases and growth factors active during wound repair can accelerate syndecan shedding from cell surfaces. Regulated shedding of syndecans suggests physiological roles for the soluble proteoglycan ectodomains. The response to tissue injury is orchestrated by multiple soluble effectors. These are derived from the blood plasma, immigrant cells from the circulation and resident cells at the wound site, and include proteases, antiproteases, growth factors, cytokines, and chemokines (1Bourin M.C. Lindahl U. Biochem. J. 1993; 289: 313-330Google Scholar). Heparin modifies the action of several of these effector molecules such as thrombin, antithrombin III, heparin-binding epidermal growth factor-like growth factor (HB-EGF), 1The abbreviations used are: HB-EGF, heparin-binding epidermal growth factor-like growth factor; EGF, epidermal growth factor; FGF-2, fibroblast growth factor-2; TGF-α, transforming growth factor-α; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; FCS, fetal calf serum; GAG, glycosaminoglycan; PMA, phorbol 12-myristate 13-acetate; TRAP, thrombin receptor agonist peptide; TPCK,l-1-tosylamido-2-phenylethyl chloromethyl ketone; CM, conditioned medium; HSE-1, serum antibody against human syndecan-1 ectodomain; AU, absorbance unit(s); PAGE, polyacrylamide gel electrophoresis; mAbs, monoclonal antibody. vascular endothelial cell growth factor, basic fibroblast growth factor, and interleukin-8 (2Bernfield M. Hinkes M.T. Biochem. J. 1993; Google Scholar, 3Bourin M.C. Lindahl U. Biochem. J. 1993; 289: 313-330Google Scholar, 4Gallo R.L. Bernfield M. Clark R.A. Molecular and Cellular Biology of Wound Repair. Plenum, New York1995: 475-492Google Scholar). These interactions focus attention on the potential regulatory role of the heparan sulfate that is at the surface of all adherent cells. Much of the heparan sulfate at the cell surface is derived from the syndecan family of transmembrane proteoglycans. These four gene products consist of single polypeptides which comprise at their COOH termini a short cytoplasmic domain (28–34 amino acids) containing three invariant tyrosines, and at their NH2 termini an extracellular domain (ectodomain) that places heparan sulfate chains distal from the plasma membrane. The syndecans bind a variety of growth factors, cytokines, proteases, antiproteases, and cell adhesion molecules (5Jalkanen M. Jalkanen S. Bernfield M. Mecham R.P. McDonald J.A. Biology of Extracellular Matrix. Receptors for Extracellular Matrix Proteins. Academic Press, Inc., Orlando, FL1991: 1-37Google Scholar, 6Bernfield M. Kokenyesi R. Kato M. Hinkes M.T. Spring J. Gallo R.L. Lose E.J. Annu. Rev. Cell Biol. 1992; 8: 365-398Google Scholar), are individually expressed in distinct cell-, tissue-, and development-specific patterns (7Kim C.W. Goldberger O.A. Gallo R.L. Bernfield M. Mol. Biol. Cell. 1994; 5: 797-805Google Scholar), and show cell-specific variations in the structure of their heparan sulfate chains (8Kato M. Wang H. Bernfield M. Gallagher J.T. Turnbull J.E. J. Biol. Chem. 1994; 269: 18881-18890Google Scholar, 9Sanderson R.D. Turnbull J.E. Gallagher J.T. Lander A.D. J. Biol. Chem. 1994; 269: 13100-13106Google Scholar). Syndecan expression is highly regulated during development, neoplasia, and wound repair (2Bernfield M. Hinkes M.T. Biochem. J. 1993; Google Scholar, 4Gallo R.L. Bernfield M. Clark R.A. Molecular and Cellular Biology of Wound Repair. Plenum, New York1995: 475-492Google Scholar, 6Bernfield M. Kokenyesi R. Kato M. Hinkes M.T. Spring J. Gallo R.L. Lose E.J. Annu. Rev. Cell Biol. 1992; 8: 365-398Google Scholar, 10Inki P. Jalkanen M. Ann. Med. 1996; 28: 63-67Google Scholar). Following skin wounds in mice, the keratinocytes at the leading edge migrating into the wound show a loss of cell surface syndecan-1. Concomitantly, syndecan-1 expression increases on the endothelial cells and syndecan-4 expression increases on the dermal fibroblasts that comprise the forming granulation tissue (11Elenius K. Vainio S. Laato M. Salmivirta M. Thesleff I. Jalkanen M. J. Cell Biol. 1991; 114: 585-595Google Scholar, 12Gallo R. Kim C. Kokenyesi R. Adzick N.S. Bernfield M. J. Invest. Dermatol. 1996; 107: 676-683Google Scholar). Cell surface syndecan-1 and -4 and their transcripts are induced in cultured endothelia and fibroblasts by PR-39, a pig neutrophil-derived antimicrobial peptide, and analogous inductive activity is found in human wound fluid (13Gallo R.L. Ono M. Povsic T. Page C. Eriksson E. Klagsbrun M. Bernfield M. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 11035-11039Google Scholar). While syndecan expression can be regulated at or following transcription, depending on the cell type or pathophysiological situation, the precise mechanism(s) underlying these changes is unknown (11Elenius K. Vainio S. Laato M. Salmivirta M. Thesleff I. Jalkanen M. J. Cell Biol. 1991; 114: 585-595Google Scholar, 14Sanderson R.D. Bernfield M. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 9562-9566Google Scholar, 15Vainio S. Jalkanen M. Vaahtokari A. Sahlberg C. M. Bernfield M. Thesleff I. Biol. 1991; Scholar, R.D. Hinkes M.T. Bernfield M. J. Invest. Dermatol. 1992; Scholar, C. A. J. Cell Biol. 1993; Scholar). of transmembrane proteins is regulated by of their ectodomains which are into the 1991; Scholar, J. A. Annu. Rev. Biochem. 1993; Scholar, S. Biochem. J. 1994; Scholar). These cell surface proteins have soluble in and can be in various fluids 1991; Scholar, M. K. Eriksson E. S. P. J. Klagsbrun M. Proc. Natl. Acad. Sci. U. S. A. 1993; Scholar). shedding can in of the of the cell surface this shedding to be a highly regulated process and a for the shedding of several transmembrane proteins by the action of or protein kinase such as phorbol 12-myristate A. J. J. Biol. Chem. 1991; Scholar, J. J. J. Cell Biol. Scholar, J. P. S. J. J. Biol. Chem. 1996; Scholar). for many that syndecan-1 is shed constitutively by cultured cells M. A. S. Bernfield M. J. Cell Biol. and that this shedding of the soluble ectodomain S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). of the syndecan family members is shed (7Kim C.W. Goldberger O.A. Gallo R.L. Bernfield M. Mol. Biol. Cell. 1994; 5: 797-805Google and the of to be a or a basic to the plasma M. Kokenyesi R. Kato M. Hinkes M.T. Spring J. Gallo R.L. Lose E.J. Annu. Rev. Cell Biol. 1992; 8: 365-398Google Scholar, M. A. S. Bernfield M. J. Cell Biol. Scholar). have found that of syndecan shedding are to of the to be for shedding of several growth factors, growth factor cell and the syndecan-1 and -4 are shed at basal but this shedding is accelerated of cells S. Jalkanen M. S. Bernfield M. J. Cell Biol. syndecan basic to the plasma is shed from cultured cells J. Bernfield M. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: Scholar). Thus, as by the the amino acid not be of to the the loss of cell surface syndecan-1 during wound repair, a process various proteases and growth factors, the that receptor can the shedding 1992; 114: Scholar, E. E. A. J. Cell Biol. 1996; Scholar, C. J. Cell Mol. Biol. 1996; Scholar). Therefore, we examined whether (i) agents that are active during acute wound repair influence syndecan shedding and (ii) dermal wound fluids contain shed find that thrombin, and epidermal growth factor family members accelerate the shedding of the syndecan-1 and -4 ectodomains from cultured endothelial cell that activation of at least two distinct receptor protein-coupled and protein tyrosine shedding, and that the syndecan and -4 ectodomains are in acute human dermal wound fluids. Regulated shedding of the syndecans suggests a physiological role for the soluble proteoglycan ectodomains. human from J. EGF, TGF-α, and from derived growth factor from vascular endothelial cell growth factor 165 from of and from thrombin thrombin receptor agonist peptide and from and from PMA, and from sulfate and sulfate from and from or to syndecan ectodomains monoclonal against the syndecan-1 ectodomain M. H. A. Bernfield M. J. Cell Biol. Scholar), and against the syndecan-4 ectodomain R. Kim C. Kokenyesi R. Adzick N.S. Bernfield M. J. Invest. Dermatol. 1996; 107: 676-683Google Scholar), and against their syndecan ectodomains (7Kim C.W. Goldberger O.A. Gallo R.L. Bernfield M. Mol. Biol. Cell. 1994; 5: 797-805Google and HSE-1, against the human syndecan-1 ectodomain R. Kim C. Kokenyesi R. Adzick N.S. Bernfield M. J. Invest. Dermatol. 1996; 107: 676-683Google Scholar). against the syndecan-1 and -4 cytoplasmic which are in and human syndecan-1 and against a acid peptide to the COOH of S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). for the syndecan-4 cytoplasmic domain against a acid peptide to the syndecan-4 cytoplasmic The the multiple peptide and used for and of at The for syndecan cytoplasmic domain by the to the syndecan family of by of SVEC4–10 cell in for of the four syndecan ectodomains and Each that these cells all four The from protein by in of in the to and and as a in the found in the Thus, is for the cytoplasmic domain of The shed of syndecan-1 and -4 from the conditioned of cells cultured for by and to the of and Bernfield A. Bernfield M. J. Biol. Chem. Scholar). of this the of heparan sulfate proteoglycan from of SVEC4–10 The transmembrane of syndecan-1 and -4 from a of cells in a The on a containing and in of this the of sulfate proteoglycan in the from cells. human dermal wound fluids and as by C. A. J. Invest. Dermatol. 1992; Google and J. Invest. Dermatol. 1993; Scholar). wound fluid at for three from in the following at for to cells and and at and Wound fluids by E. and The of this by the of the and plasma from human blood at following of on a by at for at and SVEC4–10 cells cultured in and tissue or for and to in containing at Inc., fetal calf serum and the of containing the of and Following for the cells examined by for and and the conditioned for in and or in the protein serum as the The in of The of which into three for at least three of cell surface syndecans from SVEC4–10 cell in as M. A. S. Bernfield M. J. Cell Biol. Scholar). following of the conditioned cell and of in the same for on to cells a and for at containing the ectodomains used or at for protein and from as SVEC4–10 cell conditioned and and human dermal wound fluids in to and to in an The and by a in serum in the of antibody for a syndecan ectodomain or cytoplasmic in containing and a of the in by the as by the and by the the by the containing conditioned by in The on the proteoglycans. by of the soluble syndecan-1 ectodomain M. A. S. Bernfield M. J. Cell Biol. on as an These a of absorbance and of syndecan-1. of SVEC4–10 cell conditioned used as an for the shed syndecan-4 and these a of for these in of in in of in Thus, absorbance not are expressed as the of syndecan shed in for the are for of Each the of significance the the SVEC4–10 cells at in in of for in the conditioned containing and in containing and of heparan sulfate and sulfate Inc., for at and of conditioned for syndecan-1 and to a Scholar), and to The as for the syndecan-1 and -4 core proteins and by Wound fluid and against the human syndecan-1 ectodomain or a of against the human syndecan-4 ectodomain and The protein to and to human cell cell conditioned by and A. Bernfield M. J. Biol. Chem. Scholar), as a and -4 by or and from cells by in and as in the in a to the and and in at for of a of the syndecan-1 S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). at by two at in and to an at The a of the by to the of by from whether agents to be in wound repair the shedding of syndecan ectodomains from the cell SVEC4–10 cells, a endothelial cell used as a cell M. J. Scholar). These cells in the or of syndecan-1 and and shed the ectodomains of these syndecans at a basal by the in the of syndecan ectodomains. Shed proteoglycans are not by these cells during a and are stable the conditioned not cells to shed the syndecan-1 ectodomain by that the in conditioned (i) as a core protein at the as the ectodomain M. A. S. Bernfield M. J. Cell Biol. but the transmembrane proteoglycan A. Jalkanen M. Bernfield M. Mecham R.P. Biology of Extracellular Biology of Inc., Academic Press, New Scholar), and (ii) to an antibody against the cytoplasmic domain S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). these for syndecan-1 and -4 shed into conditioned by SVEC4–10 cells in the or of serum. in conditioned and cell as to and to and to the core proteins derived from the conditioned from not The proteoglycans on and core against the ectodomains and the cytoplasmic against the syndecan-1 and -4 ectodomains these proteoglycans in cell and conditioned as against the cytoplasmic proteoglycans in the cell but to proteoglycans in conditioned that these are the ectodomains. examined the of various agents on syndecan shedding by SVEC4–10 cells during a in the and of fetal calf serum. shedding of syndecan-1 and -4 but shedding by as S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). and accelerated shedding, vascular endothelial cell growth factor FGF-2, platelet-derived growth factor and not and not growth shedding by of the cells in serum-containing thrombin and accelerate shedding, but not shedding completely inhibited by of the cells in serum-containing accelerate syndecan cells for thrombin, or in the or of fetal calf serum. by for syndecan-1 and -4 ectodomains as in members of the family accelerated the shedding of syndecan-1 and -4 from SVEC4–10 cells and the the least FGF-2, and bind this not to influence whether syndecans are shed in response to growth Thus, shedding of syndecan-1 and -4 to be a regulated and certain proteases and growth factors accelerate shedding from SVEC4–10 cells and shedding of proteoglycans is accelerated by proteases is inhibited by that serum which of the core the and growth factor accelerated shedding is not by a whether the shed ectodomains in size from SVEC4–10 cells by distinct cells for various agents in the of serum. The proteoglycans and and to and the ectodomain core proteins by The syndecan-1 and -4 ectodomain core proteins and the same size regardless whether shed at a basal rate, or accelerated by PMA, thrombin, or HB-EGF, or These that the shedding mechanism the same size whether shed constitutively or by a phorbol or growth the ectodomain the same as ectodomains by we whether syndecan shedding accelerated by thrombin from thrombin receptor activation thrombin syndecan-1 ectodomain but syndecan-4 ectodomain in the and of the syndecan-4 Thrombin receptor activation the activity of thrombin Cell. 1991; Scholar). Therefore, cells TRAP, a 14-amino acid peptide which directly activates the thrombin receptor and activity R. T. J. J. Biol. Chem. 1992; Scholar). a in the of the shed syndecan-1 and syndecan-4 ectodomains in the and Thus, activation of the thrombin receptor can accelerate syndecan-1 and -4 The of accelerated shedding during the of and shedding of syndecan-1 as as following and the of shed syndecan-1 and syndecan-4 at a cells used in these not whether these agents accelerate syndecan shedding by receptor we whether tyrosine kinase a tyrosine kinase T. J. S. H. S. M. J. Biol. Chem. and shedding of syndecan-1 and syndecan-4 the tyrosine kinase and not Thus, tyrosine is in the shedding of syndecan-1 and -4 from the cell of syndecan shedding be to several Thus, we of cell surface syndecan-1 and syndecan-1 during the of and The conditioned of and cells and syndecan-1 ectodomain cells an this in the of cell surface proteoglycan The of syndecan-1 not during accelerated These that accelerated shedding is by syndecan at the cell in SVEC4–10 or cell during accelerated shedding, an which that the cells have at least of their cell surface syndecan-1 during accelerated shedding M. S. H. Bernfield M. Mol. Biol. Cell. Scholar). wound repair in the keratinocytes migrating into the wound syndecan-1. syndecan-1 is induced on the endothelial cells and syndecan-4 on the dermal fibroblasts that comprise the forming granulation tissue (11Elenius K. Vainio S. Laato M. Salmivirta M. Thesleff I. Jalkanen M. J. Cell Biol. 1991; 114: 585-595Google Scholar, 12Gallo R. Kim C. Kokenyesi R. Adzick N.S. Bernfield M. J. Invest. Dermatol. 1996; 107: 676-683Google Scholar). thrombin, and family of syndecan-1 and -4 shedding from cultured SVEC4–10 cells, are to during acute wound repair (1Bourin M.C. Lindahl U. Biochem. J. 1993; 289: 313-330Google Scholar). Thus, we examined whether the fluids in acute wounds syndecan-1 and dermal wound fluids or for the human syndecan-4 ectodomain and and the on and by that as proteoglycans the syndecan-1 a proteoglycan and a The syndecan-1. whether the wound fluid syndecans the transmembrane proteoglycans or the the wound fluid proteoglycans on and against the ectodomains and cytoplasmic as in against the syndecan-1 and -4 ectodomains proteoglycans in acute wound but not in plasma against the cytoplasmic to these proteoglycans Thus, the syndecans in wound fluid are the shed from cell surfaces. this we show that thrombin, and members of the family accelerate shedding of the syndecan-1 and -4 ectodomains from cultured endothelial cell and that activation of at least two distinct receptor and syndecan of syndecan shedding to be and thrombin are during wound repair, and we find the shed syndecan-1 and -4 ectodomains in the fluid that acute dermal syndecan shedding is accelerated by multiple that directly or these cell surface proteoglycans have physiological roles as soluble effectors. and -4 are transmembrane proteoglycans but are into conditioned and wound fluid as soluble proteoglycans. of extracellular and of cytoplasmic that the syndecans from the conditioned and wound fluid to the ectodomains. Thus, shedding to from a process but the precise of the of the or of the have for shedding of transmembrane proteins 1991; Scholar). the structure of syndecan-1 and -4 in several that are for shedding, the and of basic to the extracellular of the plasma membrane. these proteoglycans in this to agents that accelerate and -4 to the of transmembrane proteins which and of their ectodomains into the extracellular cells are protein kinase The syndecan-1 ectodomain is shed from cultured adherent cells at a basal rate, but this shedding is by of the cells M. A. S. Bernfield M. J. Cell Biol. or phorbol of protein kinase S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). the syndecan-1 ectodomain from cell A. Bernfield M. J. Biol. Chem. Scholar). find that thrombin or the syndecan-1 and -4 ectodomain from cell and this shedding is inhibited by serum. shedding the syndecan-4 ectodomain is to the syndecan-1 Thrombin receptor activation the activity of thrombin Cell. 1991; Scholar). Thus, we whether the thrombin receptor agonist peptide, TRAP, which directly activates the receptor R. T. J. J. Biol. Chem. 1992; Scholar), accelerated the shedding of syndecan-1 and -4 ectodomains. shedding, that serum the activity for receptor activation of the receptor not activity and shedding is not inhibited by serum. Thrombin accelerate shedding of the syndecan core protein and receptor Each of the family of growth factors accelerated the shedding of syndecan-1 and -4 ectodomains from SVEC4–10 cells. Each of these growth factors of the growth to bind variety of growth factors, vascular endothelial cell growth factor FGF-2, platelet-derived growth factor and to accelerate syndecan shedding from these cells, that growth shedding from these cells is of the syndecan ectodomains is accelerated by cell proteases, activation by phorbol and interactions the thrombin and The interactions receptor activation three tyrosine kinase and and accelerated shedding of syndecan-1 and -4 ectodomains. the is multiple tyrosine and are in this regulated shedding we the of of the tyrosine kinase a role for tyrosine in accelerated syndecan The receptor is a transmembrane protein which and at tyrosine and can J. A. 1992; Scholar, H. Scholar). The thrombin receptor is a transmembrane protein that is to proteins M.C. 1994; Scholar). of receptor can a and which is to accelerate syndecan shedding S. Jalkanen M. S. Bernfield M. J. Cell Biol. Scholar). The of these is in the of tyrosine the of that this shedding is Thus, syndecan shedding several and at least two distinct of cell surface The of syndecan shedding to multiple that directly or that the ectodomains of these cell surface molecules have physiological roles as soluble proteoglycans. or the shedding of syndecan-1 and -4 ectodomains of at least for shedding, the of shed proteoglycan be for by a in the of cell surface Thus, as shedding the of syndecan-1 at the cell surface The syndecan-1 is that the increases an is that these cells a of cell surface syndecan-1 during accelerated for the of in cell during accelerated shedding, a in cell surface syndecan-1 is by in cell and of the S. Jalkanen M. Cell 1991; Scholar, S. M. H. Jalkanen M. Proc. Natl. Acad. Sci. U. S. A. 1992; Scholar, M. S. H. Bernfield M. Mol. Biol. Cell. Scholar). of cell surface syndecan cells to their shedding is that syndecan shedding is accelerated by multiple that at the cell surface is the of the to shedding of a of transmembrane proteins J. P. S. J. J. Biol. Chem. 1996; Scholar). to multiple of ectodomains at and is inhibited by the action of syndecan shedding this same to be The syndecan-1 and -4 ectodomains in human dermal wound fluid on and These syndecan ectodomains not in human plasma, that in the wound as a of the Syndecans in wound fluids a to that from cells (8Kato M. Wang H. Bernfield M. Gallagher J.T. Turnbull J.E. J. Biol. Chem. 1994; 269: 18881-18890Google R.D. Bernfield M. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 9562-9566Google Scholar), the cell from which are from keratinocytes a from cells or cells R.D. Bernfield M. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 9562-9566Google Scholar), that the endothelial cells at the wound be the of the shed syndecan ectodomains. The shed ectodomains by proteases in wound fluid (1Bourin M.C. Lindahl U. Biochem. J. 1993; 289: 313-330Google Scholar). The that accelerate syndecan shedding are to during acute wound injury is by cell activation of proteases, and of growth factors, of which syndecan The accelerated shedding that cell M. A. S. Bernfield M. J. Cell Biol. of the expressed transmembrane proteins that contain and potential Biol. 1996; Scholar). thrombin and during the blood the in tissue can accelerate the and activity of these proteases is and their to accelerate shedding be in the of fluid such as antithrombin III, and in the of shedding by and thrombin from SVEC4–10 cells the activation and which many into the EGF, HB-EGF, and (1Bourin M.C. Lindahl U. Biochem. J. 1993; 289: 313-330Google Scholar). The shedding activity of these growth factors is not inhibited by serum components. several transmembrane proteins by the shedding are in the response to tissue These proteins include the for C. M. J. Biol. 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Source: Journal of Biological Chemistry
Authors: Sukanya V. Subramanian, Marilyn L. Fitzgerald, Merton Bernfield
Institution: Harvard University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2161625600