Physical-chemical principles underlying RTK activation, and their implications for human disease

RTKs, the second largest family of membrane receptors, exert control over cell proliferation, differentiation and migration. In recent years, our understanding of RTK structure and activation in health and disease has skyrocketed. Here we describe experimental approaches used to interrogate RTKs, and we review the quantitative biophysical frameworks and structural considerations that shape our understanding of RTK function. We discuss current knowledge about RTK interactions, focusing on the role of different domains in RTK homodimerization, and on the importance and challenges in RTK heterodimerization studies. We also review our understanding of pathogenic RTK mutations, and the underlying physical-chemical causes for the pathologies.