Chapter title |
Engineering Small Molecule Responsive Split Protein Kinases
|
---|---|
Chapter number | 19 |
Book title |
Synthetic Protein Switches
|
Published in |
Methods in molecular biology, March 2017
|
DOI | 10.1007/978-1-4939-6940-1_19 |
Pubmed ID | |
Book ISBNs |
978-1-4939-6938-8, 978-1-4939-6940-1
|
Authors |
Javier Castillo-Montoya, Indraneel Ghosh |
Editors |
Viktor Stein |
Abstract |
The over 500 human protein kinases are estimated to phosphorylate at least one-third of the proteome. This posttranslational modification is of paramount importance to intracellular signaling and its deregulation is linked to numerous diseases. Deciphering the specific cellular role of a protein kinase of interest remains challenging given their structural similarity and potentially overlapping activity. In order to exert control over the activity of user-defined kinases and allow for understanding and engineering of complex signal transduction pathways, we have designed ligand inducible split protein kinases. In this approach, protein kinases are dissected into two fragments that cannot spontaneously assemble and are thus inactive. The two kinase fragments are attached to chemical inducers of dimerization (CIDs) that allow for ligand induced heterodimerization and concomitant activation of kinase activity. |
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