receptor tyrosine kinases

Meaning: An RTK is a transmembrane protein with an extracellular ligand-binding domain and an intracellular tyrosine kinase domain. In many RTKs, ligand binding brings two receptor monomers together (dimerization). The kinase domains then phosphorylate tyrosines on each other, using ATP as the phosphate donor. These phosphotyrosines act as docking sites for adaptor proteins, which activate the small G protein Ras. Ras starts the MAP kinase cascade, a chain of kinases that ends in changes in gene expression, cell growth and division. RTKs can also activate other pathways, such as PI3K. The insulin receptor is an RTK that exists as a preformed dimer, so dimerization after binding is typical but not universal.

On the MCAT: Passages describe a growth factor, a mutant receptor or a kinase inhibitor and ask for the effect on signaling. A receptor that stays active without ligand, or a hyperactive Ras, can drive uncontrolled division (oncogene reasoning). A kinase-dead receptor or a drug that blocks ATP binding stops the signal. Questions also ask you to compare RTKs with G protein-coupled receptors (GPCRs), which use heterotrimeric G proteins and second messengers like cAMP.

Common confusion: RTKs phosphorylate tyrosine, whereas many downstream kinases, such as PKA and the MAP kinases, phosphorylate serine or threonine. An RTK is not a GPCR. The receptor itself is the enzyme, and Ras is a different, small G protein downstream.