PDGF

Platelet-derived growth factors (PDGFs) are potent mitogenic factors (mitogens) that regulate cell growth and division, in connective tissue and the developing nervous system. PDGFs are secreted from many cell types including platelets, endothelial, epithelial, glial and inflammatory cells. PDGFs target a broad spectrum of mesoderm-derived cells, like fibroblasts, pericytes, smooth muscle cells, glial cells or mesangial cells. Four PDGF genes (PDGFA, PDGFB, PDGFC and PDGFD) edit 5 biologically active PDGF proteins which consist of a homodimer (PDGF-AA, PDGF-BB, PDGF-CC, and PDGF-DD) or heterodimer (PDGF-AB) of two chains. PDGFs are characterized by a highly conserved eight-cysteine residues domain termed the PDGF/VEGF homology domain. There are two cognate transmembrane receptors, PDGFRα and PDGFRβ, two distinct class III receptor tyrosine kinases. PDGFRα binds PDGF-A, -B and -C, while PDGFRβ can only be activated by PDGF-B and -D. The receptors dimerize upon ligand binding and cross-phosphorylate intracellular tyrosine residues. These phosphorylated residues serve as binding sites for downstream signaling components and activate, among others, phospholipase C γ (PLCγ), phosphatidyl inositol 3-kinase (PI3K), and JAK-STAT signaling. Overall, PDGFs exert their cellular effects by inducing homo- or heterodimeric complexes of α- and β-tyrosine kinase receptors, resulting in cell growth, chemotaxis, actin reorganization, and prevention of apoptosis.