Role of platelet-derived growth factors in angiogenesis and alveogenesis.

Platelet-derived growth factors (PGDFs) are 30-kDa dimeric proteins that exert their functions by binding to and activating PDGF receptors in the cell membrane [12, 22]. Two different PDGF monomers exist; the A chain and the B chain, and these may assemble into AA and BB homodimers as well as AB heterodimers. The two known PDGF-receptor proteins, the PDGF-α receptor (PDGF-Rα) and the β receptor (PDGF-Rβ) are both receptor tyrosine kinases and interact differentially with the PDGF molecules; PDGF-Rβ binds only the PDGF B chain with high affinity, whereas PDGF-Rα binds both chains with high affinity. Accordingly, the different PDGF dimers may bind to, dimerize and signal through different receptor pairs. Dimerization of the receptors is a prerequisite for signaling, since it allows for tyrosine phosphorylation of the intracellular part of the receptor molecules [11]. The resulting phosphotyrosine residues constitute binding sites for molecules carrying src-homology-2 (SH2) and other phosphotyrosine-binding domains. Their association with the PDGF receptor is a critical step in downstream signaling [5, 13].