Receptor tyrosine-protein kinase erbB-4 (HER4) (HER4)

Receptor tyrosine-protein kinase erbB-4 (HER4) is a member of the epidermal growth factor receptor (EGFR) family, playing a critical role in cell signaling, development, and disease. Unlike other family members, HER4 can undergo regulated intramembrane proteolysis to release a soluble intracellular domain (4ICD) that translocates to the nucleus or mitochondria, where it functions as a transcriptional co-activator or pro-apoptotic factor. It is essential for the normal development of the heart, central nervous system, and mammary glands. In oncology, HER4 is frequently mutated or overexpressed in various cancers, including melanoma, non-small cell lung cancer, and breast cancer, where it can exhibit both oncogenic and tumor-suppressive properties depending on the isoform and cellular context. The intracellular kinase domain of HER4 is a key therapeutic target for small-molecule tyrosine kinase inhibitors (TKIs) such as lapatinib and afatinib, which block its catalytic activity to inhibit downstream signaling pathways like PI3K/Akt and MAPK. However, targeting HER4 presents challenges, including potential cardiotoxicity due to its physiological role in cardiac maintenance.

Other names

ERBB4HER4p180erbB4ALS19Proto-oncogene-like protein c-ErbB-4erb-b2 receptor tyrosine kinase 4

Tyrosine kinase inhibition