VerbB proteins, also known as epidermal growth factor receptors (EGFRs), are a family of transmembrane receptor tyrosine kinases (RTKs) that play a crucial role in cell proliferation, differentiation, and survival. The VerbB family includes four members: VerbB-1 (EGFR, erbB1), VerbB-2 (HER2/neu, erbB2), VerbB-3 (HER3, erbB3), and VerbB-4 (HER4, erbB4).
These proteins are composed of an extracellular ligand-binding domain, a transmembrane region, and an intracellular domain possessing tyrosine kinase activity. The extracellular region is responsible for ligand recognition, while the intracellular region regulates downstream signaling pathways. Upon binding to specific ligands such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), and neuregulin (NRG), VerbB proteins undergo dimerization, which activates their tyrosine kinase activity.
Once activated, VerbB proteins phosphorylate specific tyrosine residues on themselves (autophosphorylation) or on other downstream signaling molecules, initiating a cascade of intracellular events. These include the activation of various signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, leading to cellular responses such as cell proliferation, survival, and migration. Dysregulation of VerbB signaling has been implicated in numerous diseases, including various types of cancers. Consequently, VerbB proteins have become important therapeutic targets, and drugs that specifically inhibit their activity, such as tyrosine kinase inhibitors, have been developed for
