Modeling the Regulation of the Kinase Domain of EGFR

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Cell division is a tightly regulated process, and if not controlled, may lead to the formation of tumors. Epidermal growth factor receptor (EGFR) is a transmembrane receptor that causes cell division in a wide range of cell types in response to several different growth factors. Mutations that activate EGFR in the absence of growth factors can contribute to cancer. The Dalton School SMART Team (Students Modeling A Research Topic) modeled EGFR using 3D printing technology. EGFR is a kinase that phosphorylates other proteins to turn them on or off. EGFR consists of an extracellular ligand‐binding domain, an anchoring intramembrane segment, a juxtamembrane connector segment, and a phosphorylating intracellular kinase domain. Generally, EGFR remains in an inactive form and becomes active when a ligand growth factor binds to the extracellular domain. Ligand binding changes the shape of the intracellular kinase domain, including the active site, turning it on. Active EGFR initiates a signaling pathway that causes cell growth and division. However, mutations in EGFR, including deletion of the extracellular domain or kinase domain point mutations, can activate EGFR in the absence of a growth factor, which may cause the formation of tumors because cells grow and divide uncontrollably. Therefore, EGFR is a potential target for cancer therapy. Supported by a grant from the Camille and Henry Dreyfus Foundation.