Platelet Factor 4 Binds to Vascular Proteoglycans and Controls Both Growth Factor Activities and Platelet Activation

J Biol Chem. 2017 Mar 10;292(10):4054-4063. doi: 10.1074/jbc.M116.760660. Epub 2017 Jan 23.

Abstract

Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation. This study revealed additional insight into the ways in which PF4 interacts with components of the vasculature to modulate cellular events.

Keywords: extracellular matrix protein; glycosaminoglycan; heparan sulfate; perlecan; proteoglycan; proteoglycan structure; serglycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / metabolism*
  • Blotting, Western
  • Chondroitin Sulfates / metabolism*
  • Dermatan Sulfate / metabolism*
  • Fibroblast Growth Factor 2 / metabolism*
  • Heparan Sulfate Proteoglycans / metabolism*
  • Heparitin Sulfate / metabolism*
  • Humans
  • Platelet Activation
  • Platelet Factor 4 / metabolism*
  • Protein Binding
  • Proteoglycans / metabolism*
  • Vesicular Transport Proteins / metabolism*

Substances

  • Heparan Sulfate Proteoglycans
  • Proteoglycans
  • Vesicular Transport Proteins
  • serglycin
  • Fibroblast Growth Factor 2
  • perlecan
  • Dermatan Sulfate
  • Platelet Factor 4
  • Chondroitin Sulfates
  • Heparitin Sulfate