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Biochemistry. 2018 Feb 27;57(8):1390-1398. doi: 10.1021/acs.biochem.7b01158. Epub 2018 Feb 6.

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase.

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Department of Chemistry & Biochemistry, University of the Sciences , Philadelphia, Pennsylvania 19104, United States.
Global Center for Pharmaceutical Ingredient Materials, Department of Applied Chemistry, Kyung Hee University , Yongin, Gyeonggi, Republic of Korea.
Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University , Seoul, Republic of Korea.
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, United States.
Departments of Molecular Biophysics and Biochemistry and Neuroscience, Yale University , New Haven, Connecticut 06520, United States.
Departments of Oncology and Biological Chemistry, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, United States.
Division of Genetics, Brigham and Women's Hospital, Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School , Boston, Massachusetts 02115, United States.


Identifying direct substrates targeted by protein kinases is important in understanding cellular physiology and intracellular signal transduction. Mass spectrometry-based quantitative proteomics provides a powerful tool for comprehensively characterizing the downstream substrates of protein kinases. This approach is efficiently applied to receptor kinases that can be precisely, directly, and rapidly activated by some agent, such as a growth factor. However, nonreceptor tyrosine kinase Abl lacks the experimental advantage of extracellular growth factors as immediate and direct stimuli. To circumvent this limitation, we combine a chemical rescue approach with quantitative phosphoproteomics to identify targets of Abl and their phosphorylation sites with enhanced temporal resolution. Both known and novel putative substrates are identified, presenting opportunities for studying unanticipated functions of Abl under physiological and pathological conditions.

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