PDGF C is a selective alpha platelet-derived growth factor receptor agonist that is highly expressed in platelet

Li Fang1, Yibing Yan, Laszlo G Komuves

  • 1Millennium Pharmaceuticals, South San Francisco, Calif 94080, USA.

Insights

Platelet-derived growth factor C (PDGF C) preferentially binds alpha PDGF receptors and is expressed in platelets. PDGF C is secreted upon platelet activation, suggesting a role in platelet biology.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Developmental Biology

Background:

  • The platelet-derived growth factor (PDGF) family comprises four members (PDGF A, B, C, D) signaling via PDGF receptor (PDGFR) tyrosine kinases.
  • PDGF C and D are newly identified members of the PDGF family.

Purpose of the Study:

  • To determine the receptor specificity of PDGF C.
  • To investigate the cellular expression profile of PDGF C.

Main Methods:

  • Western blot analysis
  • Real-time polymerase chain reaction (PCR)
  • Immuno-gold electron microscopy
  • Microarray analysis

Main Results:

  • PDGF C growth factor domain preferentially binds and activates alpha PDGFR.
  • PDGF C activates beta PDGFR when co-expressed with alpha PDGFR via heterodimer formation.
  • PDGF C is expressed in mouse fetal tissues (mesonephric mesenchyme, skeletal muscle, cardiac myoblasts, smooth muscle) and adult human smooth muscle.
  • PDGF C is expressed in vascular smooth muscle cells, renal mesangial cells, and platelets.
  • PDGF C protein is localized in platelet alpha granules and secreted upon activation as 55-kDa and 80-kDa isoforms.

Conclusions:

  • PDGF C exhibits specific binding and activation of PDGFRs.
  • PDGF C has a distinct expression pattern during development and in adult tissues, notably in smooth muscle and platelets.
  • PDGF C is present in platelets and secreted upon activation, indicating a potential role in platelet biology, similar to PDGF A and B.
Abstract

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