Growth Factor Receptors

Growth factors initiate numerous different signaling cascades in order to regulate cell differentiation and proliferation. The growth/survival signal is initially carried by these receptor ligands - proteins such as epidermal growth factor (EGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) - which bind cell-surface receptor tyrosine kinases (RTKs). Additionally, transforming growth factor β signals through receptor serine/threonine kinases (RSTKs) and activates downstream SMAD proteins to regulate the expression of specific genes.

Receptor-mediated endocytosis helps terminate the growth factor signal by internalizing the ligand-receptor complex. However, mutant RTKs may continue to send proliferative signals even in the absence of growth factor stimulation. Deregulation of growth factor receptor activity is found in nearly all epithelial tumors, and the expression of mutant forms of growth factor proteins may also lead to cancer.

Although growth factors act on different cell types, the signal pathways they initiate often overlap: for example, both EGF and FGF ensure cell survival by activating PI 3-K and MAPK cascades. These shared mechanisms have generated large amounts of interest in the field of cancer research.