Fig. 3.

Growth factor signaling may be shaped by both cell-surface and soluble HS. During homeostasis, cell-surface HSPGs provide cis-activation of growth factor signaling by stabilizing ligand-receptor interactions. In the absence of cell-surface HSPGs, this activation may be salvaged by the presence of soluble HS fragments of sufficient size and sulfation to engage growth factor ligands and receptors. In the presence of both cell-surface HSPGs and circulating HS, we hypothesize that the excess of HS sequesters ligands, attenuating downstream growth factor signaling.