Dynamic regulatory features of the protein tyrosine kinases

Biochemical Society Transactions
Neha AmatyaAmy H Andreotti

Abstract

The SRC, Abelson murine leukemia viral oncogene homolog 1, TEC and C-terminal SRC Kinase families of non-receptor tyrosine kinases (collectively the Src module kinases) mediate an array of cellular signaling processes and are therapeutic targets in many disease states. Crystal structures of Src modules kinases provide valuable insights into the regulatory mechanisms that control activation and generate a framework from which drug discovery can advance. The conformational ensembles visited by these multidomain kinases in solution are also key features of the regulatory machinery controlling catalytic activity. Measurement of dynamic motions within kinases substantially augments information derived from crystal structures. In this review, we focus on a body of work that has transformed our understanding of non-receptor tyrosine kinase regulation from a static view to one that incorporates how fluctuations in conformational ensembles and dynamic motions influence activation status. Regulatory dynamic networks are often shared across and between kinase families while specific dynamic behavior distinguishes unique regulatory mechanisms for select kinases. Moreover, intrinsically dynamic regions of kinases likely play important regul...Continue Reading

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Citations

Jun 3, 2021·International Journal of Molecular Sciences·Max Von SuskilManoj K Pandey
Aug 8, 2021·International Journal of Molecular Sciences·Balázs MerőLászló Buday
Aug 24, 2021·Current Opinion in Structural Biology·Laurel M PegramNatalie G Ahn

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