Historical Background
Protein tyrosine kinases (PTKs) are enzymes that catalyze the transfer of phosphate groups from ATP molecules to tyrosine residues of their substrates. PTKs can be divided into receptor tyrosine kinases (RTKs) and nonreceptor tyrosine kinases. In humans, there are 32 nonreceptor tyrosine kinases and 58 RTKs. RTKs can further be divided into 20 subfamilies depending on their domain arrangements (Lemmon and Schlessinger 2010). They are important components of cellular signaling pathways and regulate cell proliferation, survival, differentiation, metabolism, and motility. Because of their role in cellular signal transduction pathways, genetic changes that affect RTK activity can result in various diseases. RTKs are therefore attractive drug targets in many diseases including cancers. Among 20 RTK subfamilies, the type III receptor tyrosine kinase family, including platelet-derived growth factor receptors (PDGFA and PDGFB), colony...
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References
Agarwal S, Kazi JU, Rönnstrand L. Phosphorylation of the activation loop tyrosine 823 in c-Kit is crucial for cell survival and proliferation. J Biol Chem. 2013;288:22460–8. doi:10.1074/jbc.M113.474072.
Ashman LK. The biology of stem cell factor and its receptor C-kit. Int J Biochem Cell Biol. 1999;31:1037–51.
Blume-Jensen P, Siegbahn A, Stabel S, Heldin CH, Rönnstrand L. Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C. EMBO J. 1993;12:4199–209.
Cooper JA, Kaneko T, Li SS. Cell regulation by phosphotyrosine-targeted ubiquitin ligases. Mol Cell Biol. 2015;35:1886–97. doi:10.1128/MCB.00098-15.
Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood. 1993;82:1151–8.
DiNitto JP, Deshmukh GD, Zhang Y, Jacques SL, Coli R, Worrall JW, et al. Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. J Biochem. 2010;147:601–9. doi:10.1093/jb/mvq015.
Gommerman JL, Sittaro D, Klebasz NZ, Williams DA, Berger SA. Differential stimulation of c-Kit mutants by membrane-bound and soluble Steel Factor correlates with leukemic potential. Blood. 2000;96:3734–42.
Hayashi S, Kunisada T, Ogawa M, Yamaguchi K, Nishikawa S. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res. 1991;19:1267–71.
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141:1117–34. doi:10.1016/j.cell.2010.06.011.
Lennartsson J, Rönnstrand L. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012;92:1619–49. doi:10.1152/physrev.00046.2011.
Masson K, Rönnstrand L. Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal. 2009;21:1717–26. doi:10.1016/j.cellsig.2009.06.002.
Mayerhofer M, Gleixner KV, Hoelbl A, Florian S, Hoermann G, Aichberger KJ, et al. Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens. J Immunol. 2008;180:5466–76.
Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, et al. Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem. 2003;278:31461–4. doi:10.1074/jbc.C300186200.
Nishida K, Wang L, Morii E, Park SJ, Narimatsu M, Itoh S, et al. Requirement of Gab2 for mast cell development and KitL/c-Kit signaling. Blood. 2002;99:1866–9.
Sierra JR, Cepero V, Giordano S. Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy. Mol Cancer. 2010;9:75. doi:10.1186/1476-4598-9-75.
Sun J, Pedersen M, Rönnstrand L. Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit. J Biol Chem. 2008;283:27444–51. doi:10.1074/jbc.M709703200.
Sun J, Pedersen M, Rönnstrand L. The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction. J Biol Chem. 2009;284:11039–47. doi:10.1074/jbc.M808058200.
Turkson J. STAT proteins as novel targets for cancer drug discovery. Expert Opin Ther Targets. 2004;8:409–22. doi:10.1517/14728222.8.5.409.
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Rupar, K., Kazi, J.U., Rönnstrand, L. (2016). Kit. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101666-1
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DOI: https://doi.org/10.1007/978-1-4614-6438-9_101666-1
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