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PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor
Ludwig Institute for Cancer Research, Stockholm Branch, PO Box 240, S-171 77 Stockholm, Sweden .
Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), SF-00014 Helsinki, Finland .
Ludwig Institute for Cancer Research, Stockholm Branch, PO Box 240, S-171 77 Stockholm, Sweden .
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
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2001 (English)In: Nature Cell Biology, ISSN 1465-7392, Vol. 3, no 5, 512-516 p.Article in journal (Refereed) Published
Abstract [en]

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 alpha-receptor (PDGFR-alpha) binds to all three PDGF chains, whereas the beta-receptor (PDGFR-beta) binds only to PDGF-B. Gene-targeting studies using mice have shown that the genes for PDGF-A and PDGF-B, as well as the two PDGFR genes, are essential for normal development. Furthermore, overexpression of PDGFs is linked to different pathological conditions, including malignancies, atherosclerosis and fibroproliferative diseases. Here we have identify and characterize a fourth member of the PDGF family, PDGF-D. PDGF-D has a two-domain structure similar to PDGF-C and is secreted as a disulphide-linked homodimer, PDGF-DD. Upon limited proteolysis, PDGF-DD is activated and becomes a specific agonistic ligand for PDGFR-beta. PDGF-DD is the first known PDGFR-beta-specific ligand, and its unique receptor specificity indicates that it may be important for development and pathophysiology in several organs.

Place, publisher, year, edition, pages
Macmillan Magazines Ltd , 2001. Vol. 3, no 5, 512-516 p.
Keyword [en]
Amino Acid Sequence, Animals, Baculoviridae/metabolism, Blotting; Northern, Cloning; Molecular, Cysteine/chemistry, DNA; Complementary/metabolism, Dimerization, Dose-Response Relationship; Drug, Humans, Immunohistochemistry, Insects, Ligands, Lymphokines, Mice, Mice; Transgenic, Molecular Sequence Data, Phylogeny, Platelet-Derived Growth Factor/*chemistry, Protein Binding, Protein Structure; Tertiary, RNA; Messenger/metabolism, Receptor; Platelet-Derived Growth Factor beta/*chemistry/metabolism, Recombinant Proteins/chemistry/metabolism, Research Support; Non-U.S. Gov't, Sequence Homology; Amino Acid, Tissue Distribution
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-73351DOI: 10.1038/35074588PubMedID: 11331881OAI: oai:DiVA.org:uu-73351DiVA: diva2:101261
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2009-10-07Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11331881&dopt=Citation

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