TY - JOUR
T1 - The transition model of RTK activation
T2 - A quantitative framework for understanding RTK signaling and RTK modulator activity
AU - Paul, Michael D.
AU - Hristova, Kalina
N1 - Funding Information:
Supported by National Science foundation (NSF) MCB 1712740 , USA and National Institutes of health (NIH) GM068619 , USA. Michael D. Paul received B.S. degrees in chemistry, biochemistry, and mathematics from the University of Chicago in 2014. After graduating, he joined the Johns Hopkins Program in Molecular Biophysics for his Ph.D. His current research is focused on using quantitative florescence microscopy methods and thermodynamic modeling to understand protein-protein interactions in the plasma membrane of cells. Kalina Hristova received her B.S. and M.S. degrees in Physics from the University of Sofia, Bulgaria, and her Ph.D. degree in Mechanical Engineering and Materials Science from Duke University, USA. She did post-doctoral work at the University of California, Irvine. She is now a Professor of Materials Science and Engineering at the Institute for NanoBioTechnology at Johns Hopkins University. Dr. Hristova is the recipient of the 2007 Margaret Oakley Dayhoff award from the Biophysical Society. She was elected Fellow of the American Physical Society in 2016, and Fellow of the American Institute for Medical and Biological Engineering in 2018. The main focus of the research in her laboratory is the physical principles that underlie membrane protein folding and signal transduction across biological membranes.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Growth factor
KW - Interactions
KW - Receptor tyrosine kinase
KW - Signaling
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U2 - 10.1016/j.cytogfr.2019.10.004
DO - 10.1016/j.cytogfr.2019.10.004
M3 - Short survey
C2 - 31711797
AN - SCOPUS:85075470062
SN - 1359-6101
VL - 49
SP - 23
EP - 31
JO - Cytokine and Growth Factor Reviews
JF - Cytokine and Growth Factor Reviews
ER -