Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies.
Receptor tyrosine kinases (RTKs) conduct biochemical signals via lateral dimerization in the plasma membrane, and their transmembrane (TM) domains play an important role in the dimerization process. Here we present two models of RTK-mediated signaling, and we discuss the role of the TM domains within the framework of these two models. We summarize findings of single-amino acid mutations in RTK TM domains that induce unregulated signaling and, as a consequence, pathological phenotypes. We review the current knowledge of pathology induction mechanisms due to these mutations, focusing on the structural and thermodynamic basis of pathogenic dimer stabilization.
Li
Edwin
E
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Hristova
Kalina
K
D019943:Amino Acid Substitution; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D020022:Genetic Predisposition to Disease; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D020794:Receptor Protein-Tyrosine Kinases