6 - The Platelet-Derived Growth Factor Family

Abstract

The platelet-derived growth factor (PDGF) is a family of growth factors, which also includes VEGF. PDGFs are highly mitogenic to mesenchymal cells and are coupled with migratory behavior of mesenchymal cells, and with differentiation in developmental and adult organisms. PDGFs possess the characteristic PDGF domain composed of eight conserved cysteines, which participate in the formation of inter- and intramolecular bonds. The amino (N)-terminal region of PDGFC bears homology with the complement proteins C1r/C1s, sea urchin protein uEGF with EGF-like domains and BMP domain, which occurs in extracellular and plasma membrane-associated proteins. The carboxy (C)-terminus contains a growth factor domain (GFD), which has 25% sequence homology with VEGF and 23% homology with the PDGFA chain. Two membrane receptors, PDGFR-a and PDGFR-b, are involved in PDGF signaling. PDGF-AA, PDGF-AB, PDGF-BB, and PDGF-CC can bind to and activate PDGFR-a, PDGF-BB, and PDGF-DD specifically binds to and activates PDGFR-b. PDGF has significant influence on the biological behavior of cells that is identifiable with migratory behavior, and with differentiation in developmental and adult organisms, with cell transformation and with cancer development and progression. These phenotypic tasks are performed by well-defined systems of signal transduction coupled with interaction with signaling systems involved in the function of other growth factors. The conversion of epithelial cells into mesenchymal cells or epithelial-mesenchymal transition (EMT) is a developmental program. EMT is characterized by changes in cell morphology and reduced intercellular adhesion leading to the enhanced cell migration.