Platelet-Derived Growth Factor–BB Transactivates the Fibroblast Growth Factor Receptor to Induce Proliferation in Human Smooth Muscle Cells

Platelet-derived growth factor (PDGF) is a major stimulant for smooth muscle cell migration and proliferation, and blockade of PDGF receptors in vivo reduces intimal growth after arterial injury. Signalling by PDGF receptors has been extensively studied and involves multiple signal transduction pathways. These include ras/Extracellular Signal Regulated Kinase (ERK), a pathway critical for controlling cell cycle progression. We have recently discovered that release of fibroblast growth factor 2 and the subsequent activation of fibroblast growth factor receptor 1 are required for maximal induction by PDGF of ERK and of human smooth muscle cell proliferation. This review summarizes our latest findings and discusses the potential implications of this novel signaling mechanism for restenosis.