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Distinct heparan sulfate glycosaminoglycans are responsible for mediating fibroblast growth factor‐2 biological activity through different fibroblast growth factor receptors
Author(s) -
Berry David,
Kwan ChiPong,
Shriver Zachary,
Venkataraman Ganesh,
Sasisekharan Ram
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0661fje
Subject(s) - fibroblast growth factor , heparan sulfate , fibroblast growth factor receptor 3 , fibroblast growth factor receptor , fibroblast growth factor receptor 2 , glycosaminoglycan , fibroblast growth factor receptor 4 , microbiology and biotechnology , receptor , chemistry , fibroblast , biochemistry , biology , in vitro
Fibroblast growth factor (FGF) signaling is involved in many important biological processes such as smooth muscle cell (SMC) proliferation, a key event leading to atherosclerosis. It is well known that heparin/heparan sulfate‐like glycosaminoglycans (HLGAGs), found ubiquitously on the cell surface and in the extracellular matrix, modulate FGF signaling by interacting with both FGF and FGF receptor (FGFR). To study the modulatory effect of SMC‐derived HLGAGs on FGF2 signaling, we employed a panel of HLGAG‐degrading enzymes, or heparinases, to depolymerize cell surface HLGAGs isolated from SMCs and assayed their abilities to modulate FGF2 activity on engineered cell lines expressing defined FGFR isoforms. Our findings indicate that FGF2‐mediated proliferation is dependent on the composition of the SMC‐derived HLGAG fragments as well as the type of FGFR isoform expressed. We postulate that the chemical composition and sequence of HLGAGs dictate the specificity of interactions between FGF2 and a given FGFR.