Quantitative assessment of FGF regulation by cell surface heparan sulfates |
| |
Authors: | Berry David Shriver Zachary Venkataraman Ganesh Sasisekharan Ram |
| |
Institution: | Harvard Medical School, Boston, MA 02115, USA. |
| |
Abstract: | Heparin/heparan sulfate-like glycosaminoglycans (HSGAGs) modulate the activity of the fibroblast growth factor (FGF) family of proteins. Through interactions with both FGFs and FGF receptors (FGFRs), HSGAGs mediate FGF-FGFR binding and oligomerization leading to FGFR phosphorylation and initiation of intracellular signaling cascades. We describe a methodology to examine the impact of heparan sulfate fine structure and source on FGF-mediated signaling. Mitogenic assays using BaF3 cells transfected with specific FGFR isoforms allow for the quantification of FGF1 and FGF2 induced responses independent of conflicting influences. As such, this system enables a systematic investigation into the role of cell surface HSGAGs on FGF signaling. We demonstrate this approach using cell surface-derived HSGAGs and find that distinct HSGAGs elicit differential FGF response patterns through FGFR1c and FGFR3c. We conclude that this assay system can be used to probe the ability of distinct HSGAG species to regulate the activity of specific FGF-FGFR pairs. |
| |
Keywords: | Acidic fibroblast growth factor Basic fibroblast growth factor Heparin/heparan sulfate-like glycosaminoglycan Extracellular matrix |
本文献已被 ScienceDirect PubMed 等数据库收录! |