Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Shedding of syndecan-1 and-4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase
Autore:
Fitzgerald, ML; Wang, ZH; Park, PW; Murphy, G; Bernfield, M;
Indirizzi:
Harvard Univ, Sch Med, Div Newborn Med, Childrens Hosp, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ed, Childrens Hosp, Boston, MA 02115 USA Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England Univ E Anglia Norwich Norfolk England NR4 7TJ h NR4 7TJ, Norfolk, England
Titolo Testata:
JOURNAL OF CELL BIOLOGY
fascicolo: 4, volume: 148, anno: 2000,
pagine: 811 - 824
SICI:
0021-9525(20000221)148:4<811:SOSAEI>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPARAN-SULFATE PROTEOGLYCANS; MAMMARY EPITHELIAL-CELLS; PROTEIN-KINASE CASCADE; GROWTH-FACTOR RECEPTOR; NECROSIS-FACTOR-ALPHA; MATRIX METALLOPROTEINASE; TISSUE INHIBITOR; EXTRACELLULAR-MATRIX; PROGELATINASE-A; MOUSE EMBRYO;
Keywords:
cellular stress; heparan sulfate; mitogen-activated protein kinase; protein tyrosine kinase; proteoglycan;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
86
Recensione:
Indirizzi per estratti:
Indirizzo: Bernfield, M Harvard Univ, Sch Med, Div Newborn Med, Childrens Hosp, 300 Longwood Ave,Enders 9, Boston, MA 02115 USA Harvard Univ 300 Longwood Ave,Enders 9 Boston MA USA 02115 SA
Citazione:
M.L. Fitzgerald et al., "Shedding of syndecan-1 and-4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase", J CELL BIOL, 148(4), 2000, pp. 811-824

Abstract

The syndecan family of four transmembrane heparan sulfate proteoglycans binds a variety of soluble and insoluble extracellular effecters. Syndecan extracellular domains (ectodomains) can be shed intact by proteolytic cleavage of their core proteins, yielding soluble proteoglycans that retain the binding properties of their cell surface precursors. Shedding is accelerated by PMA activation of protein kinase C, and by ligand activation of the thrombin (G-protein-coupled) and EGF (protein tyrosine kinase) receptors (Subramanian, S.V., M.L. Fitzgerald, and M. Bernfield. 1997, J. Biol. Chem. 272:14713-14720). Syndecan-1 and -4 ectodomains are found in acute dermal wound fluids, where they regulate growth factor activity (Kato, M., H. Wang, V. Kainulainen, M.L. Fitzgerald, S. Ledbetter, D.M. Ornitz, and M. Bernfield, 1998, Nat, Men, 4:691-697) and proteolytic balance (Kainulainen, V,, H, Wang, C, Schick, and M, Bernfield. 1998, J, Biol. Chem, 273: 11563-11569). However, little is known about how syndecan ectodomain shedding is regulated. To elucidate the mechanisms that regulate syndecan shedding, we analyzed several features of the process that sheds the syndecan-1 and -4 ectodomains. We find that shedding accelerated by various physiologic agents involves activation of distinct intracellular signaling pathways; and the proteolytic activity responsible for cleavage of syndecan core proteins, which is associated with the cell surface, can act on unstimulated adjacent cells, and is specifically inhibited by TIMP-3, a matrix-associated metalloproteinase inhibitor. In addition, we find that the syndecan-1 core protein is cleavedon the cell surface at a juxtamembrane site; and the proteolytic activity responsible for accelerated shedding differs from that involved in constitutive shedding of the syndecan ectodomains. These results demonstrate the existence of highly regulated mechanisms that can rapidly convert syndecans from cell surface receptors or coreceptors to soluble heparan sulfate proteoglycan effecters. Because the shed ectodomains are found and function in vivo, regulation of syndecan ectodomain shedding by physiological mediators indicates that shedding is a response to specific developmental and pathophysiological cues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 02:46:27