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.
Objective:
The platelet-derived growth factor (PDGF) family consists of four members, PDGF A, PDGF B, and 2 new members, PDGF C and PDGF D, which signal through the alpha and beta PDGF receptor (PDGFR) tyrosine kinases. This study was performed to determine the receptor specificity and cellular expression profile of PDGF C.
Methods And Results:
PDGF C growth factor domain (GFD) was shown to preferentially bind and activate alpha PDGFR and activate beta PDGFR when it is co-expressed with alpha PDGFR through heterodimer formation. An investigation of PDGF C mRNA and protein expression revealed that during mouse fetal development, PDGF C was expressed in the mesonephric mesenchyme, prefusion skeletal muscle, cardiac myoblasts, and in visceral and vascular smooth muscle, whereas in adult human tissues expression was largely restricted to smooth muscle. Microarray analysis of various cell types showed PDGF C expression in vascular smooth muscle cells, renal mesangial cells, and platelets. PDGF C mRNA expression in platelets was confirmed by real-time polymerase chain reaction, and PDGF C protein was localized in alpha granules by immuno-gold electron microscopy. Western blot analysis of platelets identified 55-kDa and 80-kDa PDGF C isoforms that were secreted on platelet activation.
Conclusions:
Taken together, our results demonstrated for the first time to our knowledge that like PDGF A and B, PDGF C is likely to play a role in platelet biology.
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