66. Chong H, Lee J, Guan KL (2001) Positive and negative regulation of Raf kinase activity
and function by phosphorylation. EMBO J 20(14):3716–3727
67. Zhang BH, Guan KL (2000) Activation of B-Raf kinase requires phosphorylation of
the conserved residues Thr598 and Ser601. EMBO J 19(20):5429–5439
68. Diaz B et al (1997) Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory
event for Ras-dependent activation and biological signaling. Mol Cell Biol 17(8):4509–4516
69. Mason CS et al (1999) Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf
activation. EMBO J 18(8):2137–2148
70. Morrison DK, Cutler RE (1997) The complexity of Raf-1 regulation. Curr Opin Cell Biol
9(2):174–179
71. Owen JL, Lopez IE, Desai SR (2015) Cutaneous manifestations of vemurafenib therapy
for metastatic melanoma. J Drugs Dermatol 14(5):509–510
72. Young MA et al (2001) Dynamic coupling between the SH2 and SH3 domains of c-Src and
Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105(1):115–126
73. Hantschel O et al (2003) A myristoyl/phosphotyrosine switch regulates c-Abl. Cell
112(6):845–857
74. Filippakopoulos P et al (2008) Structural coupling of SH2-kinase domains links Fes and
Abl substrate recognition and kinase activation. Cell 134(5):793–803
75. Lorenz S et al (2015) Crystal structure of an SH2-kinase construct of c-Abl and effect of
the SH2 domain on kinase activity. Biochem J 468(2):283–291
76. Grebien F et al (2011) Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.
Cell 147(2):306–319
77. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm.
Nat Rev Cancer 9(3):153–166
78. Asghar U et al (2015) The history and future of targeting cyclin-dependent kinases in
cancer therapy. Nat Rev Drug Discov 14(2):130–146
79. Whittaker SR et al (2017) Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Pharmacol Ther 173:83–105
80. De Bondt HL et al (1993) Crystal structure of cyclin-dependent kinase 2. Nature
363(6430):595–602
81. Russo AA, Jeffrey PD, Pavletich NP (1996) Structural basis of cyclin-dependent
kinase activation by phosphorylation. Nat Struct Biol 3(8):696–700
82. Echalier A, Endicott JA, Noble ME (2010) Recent developments in cyclin-dependent
kinase biochemical and structural studies. Biochim Biophys Acta 1804(3):511–519
83. Brown NR et al (1999) The structural basis for specificity of substrate and recruitment
peptides for cyclin-dependent kinases. Nat Cell Biol 1(7):438–443
84. Babon JJ et al (2014) The molecular regulation of Janus kinase (JAK) activation. Biochem J
462(1):1–13
85. Boudeau J et al (2004) Analysis of the LKB1-STRAD-MO25 complex. J Cell Sci
117(Pt 26):6365–6375
86. Baas AF et al (2003) Activation of the tumour suppressor kinase LKB1 by the STE20-like
pseudokinase STRAD. EMBO J 22(12):3062–3072
87. Mehellou Y et al (2013) Structural insights into the activation of MST3 by MO25. Biochem
Biophys Res Commun 431(3):604–609
88. Zeqiraj E et al (2009) Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
mechanism of kinase activation. Science 326(5960):1707–1711
89. Zeqiraj E et al (2009) ATP and MO25alpha regulate the conformational state
of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor. PLoS
Biol 7(6):e1000126
90. Koeberle SC et al (2011) Skepinone-L is a selective p38 mitogen-activated protein kinase
inhibitor. Nat Chem Biol 8(2):141–143
Function, Structure and Topology of Protein Kinases
21
and function by phosphorylation. EMBO J 20(14):3716–3727
67. Zhang BH, Guan KL (2000) Activation of B-Raf kinase requires phosphorylation of
the conserved residues Thr598 and Ser601. EMBO J 19(20):5429–5439
68. Diaz B et al (1997) Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory
event for Ras-dependent activation and biological signaling. Mol Cell Biol 17(8):4509–4516
69. Mason CS et al (1999) Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf
activation. EMBO J 18(8):2137–2148
70. Morrison DK, Cutler RE (1997) The complexity of Raf-1 regulation. Curr Opin Cell Biol
9(2):174–179
71. Owen JL, Lopez IE, Desai SR (2015) Cutaneous manifestations of vemurafenib therapy
for metastatic melanoma. J Drugs Dermatol 14(5):509–510
72. Young MA et al (2001) Dynamic coupling between the SH2 and SH3 domains of c-Src and
Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105(1):115–126
73. Hantschel O et al (2003) A myristoyl/phosphotyrosine switch regulates c-Abl. Cell
112(6):845–857
74. Filippakopoulos P et al (2008) Structural coupling of SH2-kinase domains links Fes and
Abl substrate recognition and kinase activation. Cell 134(5):793–803
75. Lorenz S et al (2015) Crystal structure of an SH2-kinase construct of c-Abl and effect of
the SH2 domain on kinase activity. Biochem J 468(2):283–291
76. Grebien F et al (2011) Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.
Cell 147(2):306–319
77. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm.
Nat Rev Cancer 9(3):153–166
78. Asghar U et al (2015) The history and future of targeting cyclin-dependent kinases in
cancer therapy. Nat Rev Drug Discov 14(2):130–146
79. Whittaker SR et al (2017) Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Pharmacol Ther 173:83–105
80. De Bondt HL et al (1993) Crystal structure of cyclin-dependent kinase 2. Nature
363(6430):595–602
81. Russo AA, Jeffrey PD, Pavletich NP (1996) Structural basis of cyclin-dependent
kinase activation by phosphorylation. Nat Struct Biol 3(8):696–700
82. Echalier A, Endicott JA, Noble ME (2010) Recent developments in cyclin-dependent
kinase biochemical and structural studies. Biochim Biophys Acta 1804(3):511–519
83. Brown NR et al (1999) The structural basis for specificity of substrate and recruitment
peptides for cyclin-dependent kinases. Nat Cell Biol 1(7):438–443
84. Babon JJ et al (2014) The molecular regulation of Janus kinase (JAK) activation. Biochem J
462(1):1–13
85. Boudeau J et al (2004) Analysis of the LKB1-STRAD-MO25 complex. J Cell Sci
117(Pt 26):6365–6375
86. Baas AF et al (2003) Activation of the tumour suppressor kinase LKB1 by the STE20-like
pseudokinase STRAD. EMBO J 22(12):3062–3072
87. Mehellou Y et al (2013) Structural insights into the activation of MST3 by MO25. Biochem
Biophys Res Commun 431(3):604–609
88. Zeqiraj E et al (2009) Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
mechanism of kinase activation. Science 326(5960):1707–1711
89. Zeqiraj E et al (2009) ATP and MO25alpha regulate the conformational state
of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor. PLoS
Biol 7(6):e1000126
90. Koeberle SC et al (2011) Skepinone-L is a selective p38 mitogen-activated protein kinase
inhibitor. Nat Chem Biol 8(2):141–143
Function, Structure and Topology of Protein Kinases
21