Fig. 2.

Proposed mechanism by which HPSE activates VEGFR signaling. Proteins shown in gray have roles that are not fully understood. (1) Extracellular HPSE increases VEGF transcription in an SFK-dependent manner. (2) HPSE cleaves HS chains from perlecan, liberating VEGF to bind to VEGFR2 and stimulate downstream signaling. (3) HPSE activation leads to syndecan-1 shedding from the cell surface. The syndecan protein complexes with α4β1 and VEGFR2, activating the latter