PDGF-C is a new protease-activated ligand for the PDGF α-receptor

  title={PDGF-C is a new protease-activated ligand for the PDGF $\alpha$-receptor},
  author={Xuri Li and Annica Pont{\'e}n and Karin Aase and Linda Karlsson and Alexandra Abramsson and Marko Uutela and Gudrun Bäckström and Mats Hellstr{\"o}m and Hans Boström and Hong Li and Philippe Soriano and Christer Betsholtz and Carl-Henrik Heldin and Kari Alitalo and Arne {\"O}stman and Ulf Eriksson},
  journal={Nature Cell Biology},
Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF α-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the… 
PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor
PDGF-DD is the first known PDGFR-β-specific ligand, and its unique receptor specificity indicates that it may be important for development and pathophysiology in several organs.
PDGF-D, a new protease-activated growth factor
A new member of the PDGF family, PDGF D, which also requires proteolytic activation is identified and characterized, which indicates that PDGFR-α activation may result from PDG FR-α/β heterodimerization.
Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression.
TPA (tissue plasminogen activator) and matriptase as major proteases for processing of PDGF-C in MCF7 cells are identified and by site-directed mutagenesis, the cleavage site for these proteases in PD GF-C is identified.
Platelet-Derived Growth Factor
  • J. Bonner
  • Biology, Medicine
    Reference Module in Biomedical Sciences
  • 2021
Expression and function of PDGF-C in development and stem cells
The expression and functions of PDGF-C and its receptors in development and stem cells are discussed and their importance will be of great importance to various research disciplines.
Biological activities of novel Platelet-derived growth factors, PDGF-C and PDGF-D
It is suggested that PDGF-C andPDGF-D are potent modulators of vascular growth, as well as powerful mitogens for connective tissue cells for therapeutic angiogenesis and to recruit mural cells.
Platelet-derived Growth Factor C (PDGF-C), a Novel Growth Factor That Binds to PDGF α and β Receptor*
A third member of the PDGF family (PDGF-C) is described as a potent mitogen for cells of mesenchymal origin inin vitro and in vivo systems with a binding pattern similar to PDGF-AB.


Mechanism of action and in vivo role of platelet-derived growth factor.
Structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role ofPDGF in normal and diseased tissues are discussed.
Role of platelet-derived growth factors in angiogenesis and alveogenesis.
Platelet-derived growth factors are 30-kDa dimeric proteins that exert their functions by binding to and activating PDGF receptors in the cell membrane, and their association with the PDGF receptor is a critical step in downstream signaling.
Distribution and functions of platelet-derived growth factors and their receptors during embryogenesis.
Differences in binding to the solid substratum and extracellular matrix may explain isoform-specific paracrine effects of platelet-derived growth factor.
The results reveal a marked difference in the paracrine activity of PDGF-AA andPDGF-BB; the latter has a strong local growth enhancing effect, that is mostly likely to be ascribed to its association with components of the extracellular matrix.
PDGF-AA and PDGF-BB biosynthesis: proprotein processing in the Golgi complex and lysosomal degradation of PDGF-BB retained intracellularly
Findings suggest that the newly synthesized PDGF A- and B-chains are dimerized in the ER and thereafter transferred to the Golgi complex for proteolytic processing.
Not all myofibroblasts are alike: revisiting the role of PDGF‐A and PDGF‐B using PDGF‐targeted mice
The ontogeny of pericytes and alveolar SMCs suggests a common theme in the formation ofPDGF-dependent SMCs, in which PDGF-receptor positive SMC progenitors spread from proximal to distal sites along PDGF -expressing epithelial, or endothelial, tubes.
Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities.
Three recombinant homodimeric isoforms of platelet-derived growth factor were produced and purified by expression of PDGF A- and B-chains in yeast cells and stimulated growth in soft agar of human fibroblasts with PDGF-BB inducing a higher maximal response.
Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells.
Findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.
Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types.
The different abilities of the three dimeric forms of PDGF to stimulate incorporation of [3H]TdR into human fibroblasts indicated that the major mitogenic effect ofPDGF is mediated via the B type receptor.