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Article
Glycosylation Modulates Melanoma Cell α2β1 and α3β1 Integrin Interactions with Type IV Collagen
Journal of Biological Chemistry
  • Maciej J. Stawikowski, Torrey Pines Institute for Molecular Studies
  • Beatrix Aukszi, Nova Southeastern University
  • Roma Stawikowska, Torrey Pines Institute for Molecular Studies
  • Mare Cudic, Nova Southeastern University
  • Gregg B. Fields, Torrey Pines Institute for Molecular Studies
Publication Date
6-23-2014
Keywords
  • Collagen,
  • Glycosylation,
  • Hydroxylysine(Hyl),
  • Integrins,
  • Melanoma,
  • Triple-helix
Disciplines
Peer Reviewed
1
Abstract

Although type IV collagen is heavily glycosylated, the influence of this posttranslational modification on integrin binding has not been investigated. In the present study, galactosylated and non-galactosylated triple-helical peptides have been constructed containing the α1(IV)382-393 and α1(IV)531-543 sequences, which are binding sites for the α2β1 and α3β1 integrins, respectively. All peptides had triple-helical stabilities of 37 °C or greater. The galactosylation of Hyl393 in α1(IV)382-393 and Hyl540 and Hyl543 in α1(IV)531-543 had a dose dependent influence on melanoma cell adhesion which was much more pronounced in the case of α3β1 integrin binding. Molecular modeling indicated that galactosylation occurred on the periphery of α2β1 integrin interaction with α1(IV)382-393 but right in the middle of α3β1 integrin interaction with α1(IV)531-543. The possibility of extracellular deglycosylation of type IV collagen was investigated, but no β-galactosidase-like activity capable of collagen modification was found. Thus, glycosylation of collagen can modulate integrin binding, and levels of glycosylation could be altered by reduction in expression of glycosylation enzymes but most likely not by extracellular deglycosylation activity.

Comments

Copyright © 2014, The American Society for Biochemistry and Molecular Biology

DOI
10.1074/jbc.M114.572073
Citation Information
Maciej J. Stawikowski, Beatrix Aukszi, Roma Stawikowska, Mare Cudic, et al.. "Glycosylation Modulates Melanoma Cell α2β1 and α3β1 Integrin Interactions with Type IV Collagen" Journal of Biological Chemistry Vol. 289 Iss. 31 (2014) p. 21591 - 21604 ISSN: 0021-9258
Available at: http://works.bepress.com/beatrix-aukszi/9/