40. Lochhead PA et al (2006) A chaperone-dependent GSK3beta transitional intermediate
mediates activation-loop autophosphorylation. Mol Cell 24(4):627–633
41. Lochhead PA et al (2005) Activation-loop autophosphorylation is mediated by a novel
transitional intermediate form of DYRKs. Cell 121(6):925–936
42. Oliver AW, Knapp S, Pearl LH (2007) Activation segment exchange: a common mechanism
of kinase autophosphorylation? Trends Biochem Sci 32(8):351–356
43. Oliver AW et al (2006) Trans-activation of the DNA-damage signalling protein kinase Chk2
by T-loop exchange. EMBO J 25(13):3179–3190
44. Pike AC et al (2008) Activation segment dimerization: a mechanism for kinase
autophosphorylation of non-consensus sites. EMBO J 27(4):704–714
45. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell
Biol 2(2):127–137
46. Citri A, Skaria KB, Yarden Y (2003) The deaf and the dumb: the biology of ErbB-2
and ErbB-3. Exp Cell Res 284(1):54–65
47. Yarden Y, Schlessinger J (1987) Self-phosphorylation of epidermal growth factor receptor:
evidence for a model of intermolecular allosteric activation. Biochemistry 26(5):1434–1442
48. Lemmon MA, Schlessinger J, Ferguson KM (2014) The EGFR family: not so prototypical
receptor tyrosine kinases. Cold Spring Harb Perspect Biol 6(4):a020768
49. Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of
EGF receptor. Cell 110(6):669–672
50. Jura N et al (2009) Mechanism for activation of the EGF receptor catalytic domain
by the juxtamembrane segment. Cell 137(7):1293–1307
51. Jura N et al (2009) Structural analysis of the catalytically inactive kinase domain of the
human EGF receptor 3. Proc Natl Acad Sci U S A 106(51):21608–21613
52. Jura N et al (2011) Catalytic control in the EGF receptor and its connection to general
kinase regulatory mechanisms. Mol Cell 42(1):9–22
53. Zhang X et al (2006) An allosteric mechanism for activation of the kinase domain of epidermal
growth factor receptor. Cell 125(6):1137–1149
54. Endres NF et al (2013) Conformational coupling across the plasma membrane in activation
of the EGF receptor. Cell 152(3):543–556
55. Huang Y et al (2016) Molecular basis for multimerization in the activation of the epidermal
growth factor receptor. elife 5:e14107
56. Wellbrock C, Karasarides M, Marais R (2004) The RAF proteins take centre stage. Nat Rev
Mol Cell Biol 5(11):875–885
57. Brose MS et al (2002) BRAF and RAS mutations in human lung cancer and melanoma.
Cancer Res 62(23):6997–7000
58. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature
417(6892):949–954
59. Farrar MA, Alberol-Ila J, Perlmutter RM (1996) Activation of the Raf-1 kinase cascade
by coumermycin-induced dimerization. Nature 383(6596):178–181
60. Hatzivassiliou G et al (2010) RAF inhibitors prime wild-type RAF to activate the MAPK
pathway and enhance growth. Nature 464(7287):431–435
61. Weber CK et al (2001) Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res
61(9):3595–3598
62. Heidorn SJ et al (2010) Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor
progression through CRAF. Cell 140(2):209–221
63. Poulikakos PI et al (2010) RAF inhibitors transactivate RAF dimers and ERK signalling
in cells with wild-type BRAF. Nature 464(7287):427–430
64. Garnett MJ et al (2005) Wild-type and mutant B-RAF activate C-RAF through
distinct mechanisms involving heterodimerization. Mol Cell 20(6):963–969
65. Hu J et al (2013) Allosteric activation of functionally asymmetric RAF kinase dimers.
Cell 154(5):1036–1046
20
S. Röhm et al.
mediates activation-loop autophosphorylation. Mol Cell 24(4):627–633
41. Lochhead PA et al (2005) Activation-loop autophosphorylation is mediated by a novel
transitional intermediate form of DYRKs. Cell 121(6):925–936
42. Oliver AW, Knapp S, Pearl LH (2007) Activation segment exchange: a common mechanism
of kinase autophosphorylation? Trends Biochem Sci 32(8):351–356
43. Oliver AW et al (2006) Trans-activation of the DNA-damage signalling protein kinase Chk2
by T-loop exchange. EMBO J 25(13):3179–3190
44. Pike AC et al (2008) Activation segment dimerization: a mechanism for kinase
autophosphorylation of non-consensus sites. EMBO J 27(4):704–714
45. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell
Biol 2(2):127–137
46. Citri A, Skaria KB, Yarden Y (2003) The deaf and the dumb: the biology of ErbB-2
and ErbB-3. Exp Cell Res 284(1):54–65
47. Yarden Y, Schlessinger J (1987) Self-phosphorylation of epidermal growth factor receptor:
evidence for a model of intermolecular allosteric activation. Biochemistry 26(5):1434–1442
48. Lemmon MA, Schlessinger J, Ferguson KM (2014) The EGFR family: not so prototypical
receptor tyrosine kinases. Cold Spring Harb Perspect Biol 6(4):a020768
49. Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of
EGF receptor. Cell 110(6):669–672
50. Jura N et al (2009) Mechanism for activation of the EGF receptor catalytic domain
by the juxtamembrane segment. Cell 137(7):1293–1307
51. Jura N et al (2009) Structural analysis of the catalytically inactive kinase domain of the
human EGF receptor 3. Proc Natl Acad Sci U S A 106(51):21608–21613
52. Jura N et al (2011) Catalytic control in the EGF receptor and its connection to general
kinase regulatory mechanisms. Mol Cell 42(1):9–22
53. Zhang X et al (2006) An allosteric mechanism for activation of the kinase domain of epidermal
growth factor receptor. Cell 125(6):1137–1149
54. Endres NF et al (2013) Conformational coupling across the plasma membrane in activation
of the EGF receptor. Cell 152(3):543–556
55. Huang Y et al (2016) Molecular basis for multimerization in the activation of the epidermal
growth factor receptor. elife 5:e14107
56. Wellbrock C, Karasarides M, Marais R (2004) The RAF proteins take centre stage. Nat Rev
Mol Cell Biol 5(11):875–885
57. Brose MS et al (2002) BRAF and RAS mutations in human lung cancer and melanoma.
Cancer Res 62(23):6997–7000
58. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature
417(6892):949–954
59. Farrar MA, Alberol-Ila J, Perlmutter RM (1996) Activation of the Raf-1 kinase cascade
by coumermycin-induced dimerization. Nature 383(6596):178–181
60. Hatzivassiliou G et al (2010) RAF inhibitors prime wild-type RAF to activate the MAPK
pathway and enhance growth. Nature 464(7287):431–435
61. Weber CK et al (2001) Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res
61(9):3595–3598
62. Heidorn SJ et al (2010) Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor
progression through CRAF. Cell 140(2):209–221
63. Poulikakos PI et al (2010) RAF inhibitors transactivate RAF dimers and ERK signalling
in cells with wild-type BRAF. Nature 464(7287):427–430
64. Garnett MJ et al (2005) Wild-type and mutant B-RAF activate C-RAF through
distinct mechanisms involving heterodimerization. Mol Cell 20(6):963–969
65. Hu J et al (2013) Allosteric activation of functionally asymmetric RAF kinase dimers.
Cell 154(5):1036–1046
20
S. Röhm et al.