Publications by authors named "Ratika Krishnamurty"

Multidomain protein kinases, central controllers of signal transduction, use regulatory domains to modulate catalytic activity in a complex cellular environment. Additionally, these domains regulate noncatalytic functions, including cellular localization and protein-protein interactions. Src-family kinases (SFKs) are promising therapeutic targets for a number of diseases and are an excellent model for studying the regulation of multidomain kinases.

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Article Synopsis
  • Protein kinases are crucial for cell signaling and have become significant targets for drug development, necessitating tools to study their activity.
  • A novel crosslinking technique allows for the rapid and quantitative analysis of these kinases’ active sites in both cell lysates and live cells.
  • Research focused on SRC-family kinases uncovered specific inhibitors that preferentially target their inactive forms, illustrating how these inhibitors can influence regulatory interactions within the kinases.
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Article Synopsis
  • Protein kinases play a crucial role in mammalian signal transduction and are important targets for drug development.
  • The researchers have developed active site-directed probes that help profile these kinases in whole cell extracts and living cells by stabilizing a specific inactive form of kinases and allowing for their covalent modification.
  • This method successfully identified various serine/threonine and tyrosine kinases, providing valuable insights into kinase activity in realistic biological conditions.
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Affinity reagents that target protein kinases are powerful tools for signal transduction research. Here, we describe a general set of kinase ligands based on a 5-aminoindazole scaffold. This scaffold can readily be derivatized with diverse binding elements and immobilized analogs allow selective enrichment of protein kinases from complex mixtures.

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Protein kinases have emerged as one of the most frequently targeted families of proteins in drug discovery. While the development of small-molecule inhibitors that have the potency and selectivity necessary to be effective cancer drugs is still a formidable challenge, there have been several notable successes in this area over the past decade. However, in the course of the clinical use of these inhibitors, it has become apparent that drug resistance is a recurring problem.

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The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec((R)) and the recent clinical approval of a number of small molecule drugs that target protein kinases have intensified the search for novel protein kinase inhibitors. Since most small molecule kinase inhibitors target the highly conserved ATP-binding pocket of this enzyme family, the target selectivity of these molecules is a major concern. Due to the large size of the human kinome, it is a formidable challenge to determine the absolute specificity of a given protein kinase inhibitor, but recent technological developments have made substantial progress in achieving this goal.

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Synopsis of recent research by authors named "Ratika Krishnamurty"

  • - Ratika Krishnamurty's research primarily focuses on understanding the regulation and interactions of Src-family kinases (SFKs) and protein kinases, which are vital for signal transduction and are significant targets in drug discovery aimed at various diseases.
  • - Her work has advanced the development of innovative chemical proteomic tools, including affinity-based probes and active site profiling methods, that enable detailed study of kinase activity and inhibitor selectivity in complex biological environments.
  • - Krishnamurty's findings highlight important biochemical mechanisms underlying drug resistance in small-molecule protein kinase inhibitors, underscoring the challenges posed by the conserved nature of the ATP-binding pocket in these enzymes.