High-throughput Identification of FLT3 Wild-type and Mutant Kinase Substrate Preferences and Application to Design of Sensitive In Vitro Kinase Assay Substrates.

Molecular & Cellular Proteomics : MCP
Minervo PerezLaurie L Parker


Acute myeloid leukemia (AML) is an aggressive disease that is characterized by abnormal increase of immature myeloblasts in blood and bone marrow. The FLT3 receptor tyrosine kinase plays an integral role in hematopoiesis, and one third of AML diagnoses exhibit gain-of-function mutations in FLT3, with the juxtamembrane domain internal tandem duplication (ITD) and the kinase domain D835Y variants observed most frequently. Few FLT3 substrates or phosphorylation sites are known, which limits insight into FLT3's substrate preferences and makes assay design particularly challenging. We applied in vitro phosphorylation of a cell lysate digest (adaptation of the Kinase Assay Linked with Phosphoproteomics (KALIP) technique and similar methods) for high-throughput identification of substrates for three FLT3 variants (wild-type, ITD mutant, and D835Y mutant). Incorporation of identified substrate sequences as input into the KINATEST-ID substrate preference analysis and assay development pipeline facilitated the design of several peptide substrates that are phosphorylated efficiently by all three FLT3 kinase variants. These substrates could be used in assays to identify new FLT3 inhibitors that overcome resistant mutations to improve FLT3-...Continue Reading


Oct 1, 1987·Applied Biochemistry and Biotechnology·R J Linhardt
Sep 3, 2003·Nature Reviews. Cancer·Derek L Stirewalt, Jerald P Radich
Jun 29, 2004·Methods in Molecular Biology·Piotr Pozarowski, Zbigniew Darzynkiewicz
Mar 23, 2005·Nature Methods·Jessica E HuttiBenjamin E Turk
Aug 15, 2008·Journal of Proteome Research·Wilfred H TangSean L Seymour
Nov 20, 2008·British Journal of Haematology·Frank-D Böhmer, Andrea Uecker
Jul 14, 2010·Oncogene·E WeisbergJ D Griffin
Nov 1, 2011·Nature Biotechnology·Theonie AnastassiadisJeffrey R Peterson
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Liang XueW Andy Tao
May 29, 2012·Chemistry & Biology·Arminja N KettenbachScott A Gerber
Dec 4, 2012·Nucleic Acids Research·Juan Antonio VizcaínoHenning Hermjakob
Apr 25, 2013·International Journal of Hematology·Michael R Grunwald, Mark J Levis
Sep 5, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jorge E CortesMark Levis
Mar 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Catherine Choy SmithNeil P Shah
Jun 3, 2014·Therapeutic Advances in Hematology·Seth A WanderAmir T Fathi
Nov 20, 2014·Chemical Communications : Chem Comm·Wei Cui, Laurie L Parker
Jan 3, 2015·Blood·Sawa Ito, A John Barrett
Feb 7, 2015·Nature Biotechnology·Jorrit BoekelTimothy J Griffin
Feb 18, 2015·Journal of the American Chemical Society·Andrew M LipchikLaurie L Parker
Apr 20, 2017·Current Hematologic Malignancy Reports·Mark B Leick, Mark J Levis
Jun 4, 2017·Molecular Cancer Therapeutics·Maria Larrosa-Garcia, Maria R Baer
Nov 24, 2017·Protein Science : a Publication of the Protein Society·Sam L IvryCharles S Craik

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