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Mapping of matrix metalloproteinase cleavage sites on syndecan‐1 and syndecan‐4 ectodomains
Author(s) -
MaJensen Tina,
Multhaupt Hinke A. B.,
Couchman John R.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12174
Subject(s) - ectodomain , syndecan 1 , matrix metalloproteinase , microbiology and biotechnology , transmembrane protein , proteoglycan , extracellular matrix , heparan sulfate , biology , cell adhesion , transmembrane domain , chemistry , biochemistry , cell , receptor
Syndecans are transmembrane heparan sulfate proteoglycans with roles in cell proliferation, differentiation, adhesion, and migration. They have been associated with multiple functions in tumour progression, through their ability to interact with a wide range of ligands as well as other receptors, which makes them key effectors in the pericellular microenvironment. Extracellular shedding of syndecans by tumour‐associated matrix metalloproteinases ( MMP s) may have an important role in tumour progression. Such ectodomain shedding generates soluble ectodomains that may function as paracrine or autocrine effectors, or as competitive inhibitors of the intact proteoglycan. Tumour‐associated MMP s are shown here to cleave the ectodomains of human syndecan‐1 and syndecan‐4. Two membrane proximal regions of both syndecan‐1 and syndecan‐4 are favoured MMP cleavage sites, six and 15 residues from the transmembrane domain. Other sites are 35–40 residues C‐terminal from the heparan sulfate chain substitution sites in both syndecans. The MT 1‐ MMP cleavage sites in syndecan‐1 and syndecan‐4 were confirmed by site‐directed mutagenesis. These findings provide insights into the characteristics of syndecan shedding.