PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor

@article{Bergsten2001PDGFDIA,
  title={PDGF-D is a specific, protease-activated ligand for the PDGF $\beta$-receptor},
  author={E Bergsten and Marko Uutela and Xuri Li and Kristian Pietras and Arne {\"O}stman and Carl-Henrik Heldin and Kari Alitalo and Ulf Eriksson},
  journal={Nature Cell Biology},
  year={2001},
  volume={3},
  pages={512-516}
}
The term 'platelet-derived growth factor' (PDGF) refers to a family of disulphide-bonded dimeric isoforms that are important for growth, survival and function in several types of connective tissue cell. So far, three different PDGF chains have been identified — the classical PDGF-A and PDGF-B and the recently identified PDGF-C. PDGF isoforms (PDGF-AA, AB, BB and CC) exert their cellular effects by differential binding to two receptor tyrosine kinases. The PDGF α-receptor (PDGFR-α) binds to all… 
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349 Citations

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PDGF-D, a new protease-activated growth factor
TLDR
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.
The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders.
  • R. Roskoski
  • Biology, Medicine
    Pharmacological research
  • 2018
Biological activities of novel Platelet-derived growth factors, PDGF-C and PDGF-D
TLDR
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.
The PDGF family: four gene products form five dimeric isoforms.
The platelet-derived growth factor system in renal disease: an emerging role of endogenous inhibitors.
A Potential Oncogenic Activity of Platelet-Derived Growth Factor D in Prostate Cancer Progression
TLDR
It is shown that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the β-PDGF receptor and stimulates L NCaP cell proliferation in an autocrine manner, demonstrating a potential oncogenic activity of PDGFDD in the development and/or progression of prostate cancer.
Platelet-Derived Growth Factor
  • J. Bonner
  • Biology, Medicine
    Reference Module in Biomedical Sciences
  • 2021
Factor D in Prostate Cancer Progression A Potential Oncogenic Activity of Platelet-Derived Growth Updated
TLDR
It is shown that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the -PDGF receptor and stimulates L NCaP cell proliferation in an autocrine manner, demonstrating a potential oncogenic activity of PDGFDD in the development and/or progression of prostate cancer.
Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression.
TLDR
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.
Structural Requirements for Activation of Latent Platelet-derived Growth Factor CC by Tissue Plasminogen Activator*
TLDR
It is demonstrated that both the CUB and the growth factor domains of PDGF-C, as well as the kringle-2 domain of tPA, are required for the interaction and cleavage to occur, and it is shown that Arg231 in PD GF-C is essential for tPA-mediated proteolysis and that the released “free” CUB domain of PDGI can act as a competitive inhibitor of the cleavage reaction.
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References

SHOWING 1-10 OF 16 REFERENCES
PDGF-D, a new protease-activated growth factor
TLDR
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.
PDGF-C is a new protease-activated ligand for the PDGF α-receptor
TLDR
A new PDGF, PDGF-C, is identified, which binds to and activates the PDGF α-receptor and is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice.
Role of platelet-derived growth factors in angiogenesis and alveogenesis.
TLDR
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.
Mechanism of action and in vivo role of platelet-derived growth factor.
TLDR
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.
Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types.
TLDR
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.
Platelet-derived Growth Factor Receptor β Regulates Migration and DNA Synthesis in Metanephric Mesenchymal Cells*
TLDR
It is suggested that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangIAL area.
Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice.
TLDR
Results indicate that whereas the beta receptor is essential in certain cell types during embryonic development, its broader role may be masked because of compensation by the alpha-subunit.
PDGF alpha‐ and beta‐receptors activate unique and common signal transduction pathways.
TLDR
It is concluded that certain of the known PDGF induced cellular effects are transduced only by the beta‐receptor; the presence of alpha-receptor‐specific substrates suggests that there are also alpha‐recept‐specific signals, which have yet to be identified.
Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.
TLDR
It is shown that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities, and it is concluded thatPDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.
Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli.
TLDR
A model in which mesangial cells originate from PDGF-Rbeta-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response toPDGF-B during angiogenic formation of theglomerular capillary tuft is proposed.
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