PDGF-D, a new protease-activated growth factor

• Published in: Nature cell biology Vol. 3; no. 5; pp. 517 - 521
• Main Authors: LaRochelle, William J., Jeffers, Michael, McDonald, William F., Chillakuru, Rajeev A., Giese, Neill A., Lokker, Nathalie A., Sullivan, Carol, Boldog, Ferenc L., Yang, Meijia, Vernet, Corine, Burgess, Catherine E., Fernandes, Elma, Deegler, Lisa L., Rittman, Beth, Shimkets, Juliette, Shimkets, Richard A., Rothberg, Jonathan M., Lichenstein, Henri S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2001; Nature Publishing Group
• Subjects: 3T3 Cells; Amino Acid Sequence; Amino acids; Animals; Base Sequence; Binding, Competitive; Biomedical and Life Sciences; Blood platelets; brief-communication; Bromodeoxyuridine - metabolism; Cancer Research; Cell Biology; Deoxyribonucleic acid; Developmental Biology; Dimerization; DNA; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Fibroblasts - metabolism; Gene expression; Humans; Life Sciences; Lymphokines; Mice; Molecular Sequence Data; Phosphorylation; Physiological aspects; Physiology; Platelet-derived growth factor; Platelet-Derived Growth Factor - chemistry; Platelet-Derived Growth Factor - physiology; platelet-derived growth factor D; Polymerase Chain Reaction; Receptors; Receptors, Platelet-Derived Growth Factor - metabolism; Recombinant Proteins - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Stem Cells; Tissue Distribution; Tumor Cells, Cultured; Tyrosine - metabolism; Vascular endothelial growth factor; United States; United States > US; Connecticut
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/35074593

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes 1 , 2 , 3 , 4 , 5 , as well as in human cancer, fibrotic diseases and arteriosclerosis 6 . The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C 7 , 8 , a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-α 7 , 9 , 10 , whereas PDGF-B activates both PDGFR-α and PDGFR-β 9 , 11 . Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-β but not PDGFR-α. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-α activation may result from PDGFR-α/β heterodimerization.