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- W2898480197 abstract "Receptor tyrosine kinases (RTKs) are cell surface receptors which control cell growth and differentiation, and play important roles in tumorigenesis. Despite decades of RTK research, the mechanism of RTK activation in response to their ligands is still under debate. Here, we investigate the interactions that control the activation of the tropomyosin receptor kinase (Trk) family of RTKs in the plasma membrane, using a FRET-based methodology. The Trk receptors are expressed in neuronal tissues, and guide the development of the central and peripheral nervous systems during development. We quantify the dimerization of human Trk-A, Trk-B, and Trk-C in the absence and presence of their cognate ligands: human β-nerve growth factor, human brain-derived neurotrophic factor, and human neurotrophin-3, respectively. We also assess conformational changes in the Trk dimers upon ligand binding. Our data support a model of Trk activation in which (1) Trks have a propensity to interact laterally and to form dimers even in the absence of ligand, (2) different Trk unliganded dimers have different stabilities, (3) ligand binding leads to Trk dimer stabilization, and (4) ligand binding induces structural changes in the Trk dimers which propagate to their transmembrane and intracellular domains. This model, which we call the ‘transition model of RTK activation,’ may hold true for many other RTKs." @default.
- W2898480197 created "2018-11-02" @default.
- W2898480197 creator A5000748364 @default.
- W2898480197 creator A5076185298 @default.
- W2898480197 date "2018-11-30" @default.
- W2898480197 modified "2023-09-30" @default.
- W2898480197 title "Dimerization of the Trk receptors in the plasma membrane: effects of their cognate ligands" @default.
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- W2898480197 doi "https://doi.org/10.1042/bcj20180637" @default.
- W2898480197 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6918676" @default.
- W2898480197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30366959" @default.
- W2898480197 hasPublicationYear "2018" @default.
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