Receptor tyrosine kinases

Receptor tyrosine kinases (RTKs) are high-affinity cell surface receptors for many growth factors, cytokines, and hormones. Of the 90 tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins.  All RTKs share a similar protein structure comprised of an extracellular ligand binding domain, a single transmembrane helix, and an intracellular region that contains a juxtamembrane regulatory region, a tyrosine kinase domain and a carboxyl terminal tail.   Receptor tyrosine kinases are inactive in the absense of a ligand and are activated by receptor specific ligands binding to extracellular regions of RTKs, which causes receptor dimerization and/or oligomerization, allowing the tyrosine kinase domain to assume an active conformation.  Receptor tyrosine kinases play an important role in in mediating and controlling a wide range of complex biological functions, including cell growth, cell-to-cell communication, motility, differentiation, and metabolism. Consequently dysregulation of RTK signaling leads to an assortment of human diseases, including having a critical role in the development and progression of many types of cancer.

Further reading

Robinson et al (2000) The protein tyrosine kinase family of the human genome. Oncogene 19(49) 5548 PMID: 11114734

Lemmon and Schlessinger (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7) 1117 PMID: 20602996

Du and Lovly (2018) Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 17 58  https://doi.org/10.1186/s12943-018-0782-4