Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation (original) (raw)

• Rajakulendran, T., Sahmi, M., Lefrancois, M., Sicheri, F. & Therrien, M. A dimerization-dependent mechanism drives RAF catalytic activation. Nature 461, 542–545 (2009).
  Article CAS Google Scholar
• Zhang, B.H. & Guan, K.L. Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601. EMBO J. 19, 5429–5439 (2000).
  Article CAS Google Scholar
• Chong, H., Lee, J. & Guan, K.L. Positive and negative regulation of Raf kinase activity and function by phosphorylation. EMBO J. 20, 3716–3727 (2001).
  Article CAS Google Scholar
• Freeman, A.K., Ritt, D.A. & Morrison, D.K. Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling. Mol. Cell 49, 751–758 (2013).
  Article CAS Google Scholar
• Wan, P.T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855–867 (2004).
  Article CAS Google Scholar
• Heidorn, S.J. et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140, 209–221 (2010).
  Article CAS Google Scholar
• Poulikakos, P.I., Zhang, C., Bollag, G., Shokat, K.M. & Rosen, N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464, 427–430 (2010).
  Article CAS Google Scholar
• Hatzivassiliou, G. et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464, 431–435 (2010).
  Article CAS Google Scholar
• Garnett, M.J. & Marais, R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6, 313–319 (2004).
  Article CAS Google Scholar
• Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature 502, 333–339 (2013).
  Article CAS Google Scholar
• Forbes, S.A. et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39, D945–D950 (2011).
  Article CAS Google Scholar
• Zhang, X., Gureasko, J., Shen, K., Cole, P.A. & Kuriyan, J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125, 1137–1149 (2006).
  Article CAS Google Scholar
• Shi, F., Telesco, S.E., Liu, Y., Radhakrishnan, R. & Lemmon, M.A. ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc. Natl. Acad. Sci. USA 107, 7692–7697 (2010).
  Article CAS Google Scholar
• Jeffrey, P.D. et al. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 376, 313–320 (1995).
  Article CAS Google Scholar
• Tsai, J. et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl. Acad. Sci. USA 105, 3041–3046 (2008).
  Article CAS Google Scholar
• Bollag, G. et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596–599 (2010).
  Article CAS Google Scholar
• De Bondt, H.L. et al. Crystal structure of cyclin-dependent kinase 2. Nature 363, 595–602 (1993).
  Article CAS Google Scholar
• Kornev, A.P., Haste, N.M., Taylor, S.S. & Eyck, L.F. Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Proc. Natl. Acad. Sci. USA 103, 17783–17788 (2006).
  Article CAS Google Scholar
• Lavoie, H. et al. Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization. Nat. Chem. Biol. 9, 428–436 (2013).
  Article CAS Google Scholar
• Luo, Z. et al. Oligomerization activates c-Raf-1 through a Ras-dependent mechanism. Nature 383, 181–185 (1996).
  Article CAS Google Scholar
• Weber, C.K., Slupsky, J.R., Kalmes, H.A. & Rapp, U.R. Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res. 61, 3595–3598 (2001).
  CAS PubMed Google Scholar
• Röring, M. et al. Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling. EMBO J. 31, 2629–2647 (2012).
  Article Google Scholar
• Poulikakos, P.I. et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 480, 387–390 (2011).
  Article CAS Google Scholar
• Shan, Y. et al. Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization. Cell 149, 860–870 (2012).
  Article CAS Google Scholar
• Arkhipov, A. et al. Architecture and membrane interactions of the EGF receptor. Cell 152, 557–569 (2013).
  Article CAS Google Scholar
• Endres, N.F. et al. Conformational coupling across the plasma membrane in activation of the EGF receptor. Cell 152, 543–556 (2013).
  Article CAS Google Scholar
• Tran, N.H., Wu, X. & Frost, J.A. B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms. J. Biol. Chem. 280, 16244–16253 (2005).
  Article CAS Google Scholar
• Chong, H. & Guan, K.L. Regulation of Raf through phosphorylation and N terminus-C terminus interaction. J. Biol. Chem. 278, 36269–36276 (2003).
  Article CAS Google Scholar
• Wenglowsky, S. et al. Pyrazolopyridine inhibitors of B-Raf(V600E). Part 1: the development of selective, orally bioavailable, and efficacious inhibitors. ACS Med. Chem. Lett. 2, 342–347 (2011).
  Article CAS Google Scholar
• Vonrhein, C. et al. Data processing and analysis with the autoPROC toolbox. Acta Crystallogr. D Biol. Crystallogr. 67, 293–302 (2011).
  Article CAS Google Scholar
• Adams, P.D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).
  Article CAS Google Scholar
• Emsley, P., Lohkamp, B., Scott, W.G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).
  Article CAS Google Scholar
• Douziech, M. et al. Bimodal regulation of RAF by CNK in Drosophila. EMBO J. 22, 5068–5078 (2003).
  Article CAS Google Scholar
• McKay, M.M. & Morrison, D.K. Proteomic analysis of scaffold proteins in the ERK cascade. Methods Mol. Biol. 661, 323–334 (2010).
  Article CAS Google Scholar