The transition model of RTK activation: A quantitative framework for understanding RTK signaling and RTK modulator activity

Here, we discuss the transition model of receptor tyrosine kinase (RTK) activation, which is derived from biophysical investigations of RTK interactions and signaling. The model postulates that (1) RTKs can interact laterally to form dimers even in the absence of ligand, (2) different unliganded RTK dimers have different stabilities, (3) ligand binding stabilizes the RTK dimers, and (4) ligand binding causes structural changes in the RTK dimer. The model is grounded in the principles of physical chemistry and provides a framework to understand RTK activity and to make predictions in quantitative terms. It can guide basic research aimed at uncovering the mechanism of RTK activation and, in the long run, can empower the search for modulators of RTK function.