ErbB

ErbB is a family of proteins that includes four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR). The ErbB protein family or EGFR family consists of four members: ErbB1, also known as EGFR; ErbB2, also known as HER2/neu; ErbB3, also known as HER3; and ErbB4, also known as HER4.

Structure and Function

The ErbB proteins are embedded in the cell membrane and have a binding site on the outside of the cell. These proteins play a crucial role in the growth and differentiation of cells. They are activated by specific ligands, such as epidermal growth factor (EGF) and neuregulin, which bind to the extracellular domain of the receptor.

Upon ligand binding, the receptors form homodimers or heterodimers, which leads to the activation of the intracellular kinase domain. This activation triggers a series of phosphorylation events and initiates multiple downstream signaling pathways, including the PI3K/AKT/mTOR pathway, the RAS/RAF/MEK/ERK pathway, and the phospholipase C pathway. These pathways regulate various cellular processes, such as cell proliferation, cell survival, angiogenesis, and cell migration.

Clinical Significance

Abnormalities in the ErbB signaling pathways, such as overexpression or mutation of the receptors, are associated with the development of various types of cancer, including breast cancer, lung cancer, and colorectal cancer. For example, overexpression of ErbB2 (HER2/neu) is found in approximately 20-30% of breast cancers and is associated with aggressive disease and poor prognosis.

Several targeted therapies have been developed to inhibit the ErbB receptors or their downstream signaling pathways. These include monoclonal antibodies, such as trastuzumab (Herceptin) and cetuximab (Erbitux), and small molecule tyrosine kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa).

See Also

• Epidermal growth factor receptor
• Tyrosine kinase
• Targeted therapy
• Cancer