Nature Cell Biology
3, 517 - 521 (2001)
Published online: 11 April 2001; | doi:10.1038/35074593
PDGF-D, a new protease-activated growth factorWilliam J. LaRochelle1, Michael Jeffers1, William F. McDonald1, Rajeev A. Chillakuru1, Neill A. Giese2, Nathalie A. Lokker2, Carol Sullivan2, Ferenc L. Boldog1, Meijia Yang1, Corine Vernet1, Catherine E. Burgess1, Elma Fernandes1, Lisa L. Deegler1, Beth Rittman1, Juliette Shimkets1, Richard A. Shimkets1, Jonathan M. Rothberg1
& Henri S. Lichenstein11
CuraGen Corporation, 555 Long Wharf Drive, New Haven, Connecticut 06511, USA, and 322 East Main Street, Branford, Connecticut 06405, USA
2
COR Therapeutics, 256 East Grand Avenue, South San Francisco, California 94080, USA
Correspondence should be addressed to William J. LaRochelle wlarochelle@curagen.comPlatelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes1,
2,
3,
4,
5, as well as in human cancer, fibrotic diseases and arteriosclerosis6. 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-C7,
8, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR- 7,
9,
10, whereas PDGF-B activates both PDGFR- and PDGFR- 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- but not PDGFR-. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR- activation may result from PDGFR-/ heterodimerization.
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