HER2HER3

HER2HER3 refers to the heterodimerization of two receptor tyrosine kinases, HER2 and HER3. These receptors are part of the ErbB family of proteins, which play crucial roles in cell growth, proliferation, and survival. While HER2 is a potent signaling molecule, HER3 has a very weak kinase activity. However, HER3 is an exceptionally strong ligand-binding subunit for heregulin.

The formation of the HER2HER3 heterodimer is a significant signaling pathway in many cancers. When heregulin binds to HER3, it induces a conformational change that promotes the association of HER3 with HER2. This interaction leads to the transphosphorylation of HER3 by HER2. The activated HER2HER3 complex then recruits adapter proteins, such as the Grb2-SOS complex, which in turn activates downstream signaling pathways like the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This pathway is a major driver of cell survival and proliferation.

The HER2HER3 signaling axis is frequently overexpressed or activated in various cancers, including breast, ovarian, and lung cancers. Its dysregulation contributes to tumor growth, invasion, and resistance to therapy. Consequently, HER2HER3 has become a target for therapeutic interventions. Various strategies, including monoclonal antibodies and tyrosine kinase inhibitors, are employed to block this signaling pathway and inhibit cancer progression. Understanding the intricate mechanisms of HER2HER3 heterodimerization is vital for developing more effective anti-cancer treatments.