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Cytokine Growth Factor Rev. 2018 Feb;39:124-136. doi: 10.1016/j.cytogfr.2017.12.003. Epub 2017 Dec 22.

Dually modified transmembrane proteoglycans in development and disease.

Author information

1
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA. Electronic address: Lauramj@email.sc.edu.
2
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA. Electronic address: Horst@email.sc.edu.
3
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA. Electronic address: carlyll@email.sc.edu.
4
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA; Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, 29208, USA. Electronic address: Mythreye@sc.edu.

Abstract

Aberrant cell signaling in response to secreted growth factors has been linked to the development of multiple diseases, including cancer. As such, understanding mechanisms that control growth factor availability and receptor-growth factor interaction is vital. Dually modified transmembrane proteoglycans (DMTPs), which are classified as cell surface macromolecules composed of a core protein decorated with covalently linked heparan sulfated (HS) and/or chondroitin sulfated (CS) glycosaminoglycan (GAG) chains, provide one type of regulatory mechanism. Specifically, DMTPs betaglycan and syndecan-1 (SDC1) play crucial roles in modulating key cell signaling pathways, such as Wnt, transforming growth factor-β and fibroblast growth factor signaling, to affect epithelial cell biology and cancer progression. This review outlines current and potential functions for betaglycan and SDC1, with an emphasis on comparing individual roles for HS and CS modified DMTPs. We highlight the mutual dependence of DMTPs' GAG chains and core proteins and provide comprehensive knowledge on how these DMTPs, through regulation of ligand availability and receptor internalization, control cell signaling pathways involved in development and disease.

KEYWORDS:

Betaglycan; Cancer; Cell signaling; Glycosaminoglycan; Proteoglycan; Syndecan

PMID:
29291930
PMCID:
PMC5866756
DOI:
10.1016/j.cytogfr.2017.12.003
[Indexed for MEDLINE]
Free PMC Article

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