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- Title
PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor.
- Authors
Bergsten, Erika; Uutela, Marko; Li, Xuri; Pietras, Kristian; Östman, Arne; Heldin, Carl-Henrik; Alitalo, Kari; Eriksson, Ulf
- Abstract
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[SUP1,2] and the recently identified PDGF-C[SUP3]. 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 three PDGF chains, whereas the β-receptor (PDGFR-β) binds only to PDGF-B[SUP1]. 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[SUP4]. Furthermore, overexpression of PDGFs is linked to different pathological conditions, including malignancies, atherosclerosis and fibroproliferative diseases[SUP1]. 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[SUP3] 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-β. 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.
- Subjects
PLATELET-derived growth factor; DEVELOPMENTAL biology; GROWTH; TISSUE culture
- Publication
Nature Cell Biology, 2001, Vol 3, Issue 5, p512
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/35074588