The platelet-derived growth factor (PDGF) family consists of proteins derived from four genes (PDGF-A, -B, -C, and -D) that form disulfide-linked homodimers (PDGF-AA, -BB, -CC, and -DD) and a heterodimer (PDGF-AB) (1, 2). These proteins regulate diverse cellular functions by binding to and inducing the homo- or hetero-dimerization of two receptors (PDGF R alpha and R beta). Whereas alpha/ alpha homo-dimerization is induced by PDGF-AA, -BB, -CC, and -AB, alpha/ beta hetero-dimerization is induced by PDGF-AB, -BB, -CC, and -DD, and beta/ beta homo-dimerization is induced only by PDGF-BB, and -DD (1 - 4). Both PDGF R alpha and R beta are members of the class III subfamily of receptor tyrosine kinases (RTK) that also includes the receptors for M-CSF, SCF and Flt3-ligand. All class III RTKs are characterized by the presence of five immunoglobulin-like domains in their extracellular region and a split kinase domain in their intracellular region. Ligand-induced receptor dimerization results in autophosphorylation in trans resulting in the activation of several intracellular signaling pathways that can lead to cell proliferation, cell survival, cytoskeletal rearrangement, and cell migration. Many cell types, including fibroblasts and smooth muscle cells, express both the alpha and beta receptors. Others have only the alpha receptors (oligodendrocyte progenitor cells, mesothelial cells, liver sinusoidal endothelial cells, astrocytes, platelets and megakaryocytes) or only the beta receptors (myoblasts, capillary endothelial cells, pericytes, T cells, myeloid hematopoietic cells and macrophages). A soluble PDGF R alpha has been detected in normal human plasma and serum as well as in the conditioned medium of the human osteosarcoma cell line MG-63 (5). Both the recombinant mouse and human soluble PDGF R alpha bind PDGF with high affinity and are potent PDGF antagonists.