Signaling: Receptor Tyrosine Kinases

Major families of growth factor receptors are the tyrosine kinases, the small G-protein-coupled receptors (GPCRs), and the serine/threonine kinases. Tyrosine phosphorylation is considered one of the most characteristic features of several growth factors. Receptors for EGF, TGF-β, PDGF, and FGF contain a polypeptide domain with tyrosine kinase activity. Binding of growth factors to the receptors on quiescent cells leads to the activation of intrinsic receptor-associated tyrosine kinase activity and concomitant phosphorylation of tyrosine residues of cellular proteins.

The EGF receptor (EGFR) typifies the tyrosine kinase family of growth factor receptors. Nearly all tyrosine kinase receptors described thus far are composed of an extracellular ligand-binding domain, a single transmembrane domain, a region containing the tyrosine kinase activity, and a carboxy terminus extending into the cytoplasm. Within the tyrosine kinase domain of the EGF-receptor are amino acid residues that are conserved in all protein kinases and are thought to be involved in the binding of the ATP substrate.