title: Structural alteration of cell surface heparan sulfate through the stimulation of the signaling pathway for heparan sulfate 6-O-sulfotransferase-1 in mouse fibroblast cells.
abstract: Heparan sulfate (HS) is a randomly sulfated polysaccharide that is present on the cell surface and in the extracellular matrix. The sulfated structures of HS were synthesized by multiple HS sulfotransferases, thereby regulating various activities such as growth factor signaling, cell differentiation, and tumor metastasis. Therefore, if the sulfated structures of HS could be artificially controlled, those manipulations would help to understand the various functions depending on HS. However, little knowledge is currently available to realize the mechanisms controlling the expression of such enzymes. In this study, we found that the ratio of 6-O-sulfated disaccharides increased at 3 h after adrenaline stimulation in mouse fibroblast cells. Furthermore, adrenaline-induced up-regulation of HS 6-O-sulfotransferase-1 (6-OST-1) was controlled by Src-ERK1/2 signaling pathway. Finally, inhibiting the signaling pathways for 6-OST-1 intentionally suppressed the adrenaline-induced structural alteration of HS. These observations provide fundamental insights into the understanding of structural alterations in HS by extracellular cues.
authors.affiliation: a United Graduate School of Agricultural Science, Gifu University , Gifu , Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Nishida
authors.forename: Takeru
authors.initials: T
authors.lastname: Kozakai
authors.forename: Keitaro
authors.initials: K
authors.lastname: Nagami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanamaru
authors.forename: Tomio
authors.initials: T
authors.lastname: Yabe
mesh_terms: D000818:Animals; D002460:Cell Line; D004187:Disaccharides / Q000032:analysis; D004837:Epinephrine / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004187:Disaccharides; D004837:Epinephrine; D005346:Fibroblast Growth Factors; D006497:Heparan Sulfate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D015238:Sulfotransferases; C404189:heparan sulfate 6-O-sulfotransferase
keywords: 6-O-sulfotransferase-1; adrenaline; extracellular-related kinase (ERK) 1/2; heparan sulfate; signal transduction