Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase with important roles in many cellular processes as well as in cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. How these dimers relate to higher-order EGFR oligomers seen in cell membranes, however, remains unclear.

Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) with important roles in many cellular processes as well as cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. However, it is not clear how these dimers relate to higher-order EGFR oligomers detected at the cell surface.

Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias.

The epidermal growth factor receptor (EGFR) is frequently mutated in human cancer, and is an important therapeutic target. EGFR inhibitors have been successful in lung cancer, where mutations in the intracellular tyrosine kinase domain activate the receptor, but not in glioblastoma multiforme (GBM), where mutations occur exclusively in the extracellular region. Here we show that common extracellular GBM mutations prevent EGFR from discriminating between its activating ligands.

Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB.

The tropomyosin-related kinase (Trk) family consists of three receptor tyrosine kinases (RTKs) called TrkA, TrkB, and TrkC. These RTKs are regulated by the neurotrophins, a class of secreted growth factors responsible for the development and function of neurons. The Trks share a high degree of homology and utilize overlapping signaling pathways, yet their signaling is associated with starkly different outcomes in certain cancers.