Multisite protein phosphorylation - From molecular mechanisms to kinetic models

FEBS Journal

Volumn 276, Issue 12, 2009, Pages 3177-3198

  Salazar, Carlos ^a   Höfer, Thomas ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Enzyme processivity; Kinetic proofreading; Mathematical models; Order of phospho site processing; Ultrasensitivity

Indexed keywords

MEMBRANE RECEPTOR; TRANSCRIPTION FACTOR;

BIOLOGICAL MODEL; CELL COMPARTMENTALIZATION; CELL CYCLE REGULATION; CELL MEMBRANE TRANSPORT; CELL NUCLEUS; CELL SYNCHRONIZATION; COMPETITIVE INHIBITION; CONFORMATIONAL TRANSITION; HUMAN; KINETICS; MATHEMATICAL MODEL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; QUANTITATIVE ANALYSIS; REVIEW; SENSITIVITY AND SPECIFICITY; THEORETICAL MODEL;

ANIMALS; BINDING SITES; HUMANS; KINETICS; MODELS, BIOLOGICAL; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN KINASES; PROTEINS; SUBSTRATE SPECIFICITY;

EID: 66249102308     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2009.07027.x     Document Type: Review

References (133)

1. Cohen P (2001) The role of protein phosphorylation in human health and disease. The Sir Hans Krebs Medal Lecture. Eur J Biochem 268, 5001 5010.
2. Lienhard GE (2008) Non-functional phosphorylations? Trends Biochem Sci 33, 351 352.
3. Manning G, Whyte DB, Martinez R, Hunter T Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298, 1912 1934. (Pubitemid 35425239)
4. Yang XJ (2005) Multisite protein modification and intramolecular signaling. Oncogene 24, 1653 1662. (Pubitemid 40461122)
5. Cohen P (2000) The regulation of protein function by multisite phosphorylation - a 25 year update. Trends Biochem Sci 25, 596 601.
6. Holmberg CI, Tran SEF, Eriksson JE Sistonen L (2002) Multisite phosphorylation provides sophisticated regulation of transcription factors. Trends Biochem Sci 27, 619 627. (Pubitemid 35435311)
7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P Mann M (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635 648. (Pubitemid 44647421)
8. Mann M, Ong SE, Grønberg M, Steen H, Jensen ON Pandey A (2002) Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome. Trends Biotechnol 20, 261 268. (Pubitemid 34451062)
9. Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103, 211 225.
10. Acuto O, Bartolo VD Michel F (2008) Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nat Rev Immunol 8, 699 712.
11. Mohapatra DP, Park KS Trimmer JS (2002) Dynamic regulation of the voltage-gated Kv2.1 potassium channel by multisite phosphorylation. Biochem Soc Trans 35, 1064 1068.
12. Markevich NI, Hoek JB Kholodenko BN (2004) Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol 164, 353 359. (Pubitemid 38174763)
13. Huang CY Ferrell JE Jr. (1996) Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 93, 10078 10083. (Pubitemid 26314577)
14. Ingley E (2008) Src family kinases: regulation of their activities, levels and identification of new pathways. Biochim Biophys Acta 1784, 56 65.
15. Wu JN Koretzky GA (2004) The SLP-76 family of adapter proteins. Semin Immunol 16, 379 393. (Pubitemid 39488019)
16. Amarasinghe GK Rosen MK (2005) Acidic region tyrosines provide access points for allosteric activation of the autoinhibited Vav1 Dbl homology domain. Biochemistry 44, 15257 15268. (Pubitemid 41681460)
17. Lin J Weiss A (2001) Identification of the minimal tyrosine residues required for linker for activation of T cell function. J Biol Chem 276, 29588 29595. (Pubitemid 37452058)
18. Nash P, Tang X, Orlicky S, Chen Q, Gertler FB, Mendenhall MD, Sicheri F, Pawson T Tyers M (2001) Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature 414, 514 521. (Pubitemid 33131529)
19. Hutchins JR Clarke PR (2004) Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C phosphatase. Cell Cycle 3, 41 45. (Pubitemid 40268585)
20. Tak YS, Tanaka Y, Endo S, Kamimura Y Araki H (2006) A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. EMBO J 25, 1987 1996.
21. Brunner M Schafmeier T (2006) Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora. Genes Dev 20, 1061 1074.
22. Komeili A O'Shea EK (1999) Roles of phosphorylation sites in regulating activity of the transcription factor Pho4. Science 284, 977 980. (Pubitemid 29288439)
23. Okamura H, Aramburu J, Garcia-Rodriguez C, Viola JPB, Raghavan A, Tahiliani M, Zhang X, Qin J, Hogan PG, Rao A (2000) Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol Cell 6, 539 550.
24. Jonker HR, Wechselberger RW, Pinkse M, Kaptein R Folkers GE (2006) Gradual phosphorylation regulates PC4 coactivator function. FEBS J 273, 1430 1444. (Pubitemid 44055059)
25. Phatnani HP Greenleaf AL (2006) Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev 20, 2922 2936.
26. Cheung P, Tanner KG, Cheung WL, Sassone-Corsi P, Denu JM Allis CD (2000) Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol Cell 5, 905 915.
27. Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, Ghosh G Adams JA (2003) Processive phosphorylation of alternative splicing factor/splicing factor 2. Proc Natl Acad Sci USA 100, 12601 12606. (Pubitemid 37339945)
28. Bluthgen N, Bruggeman FJ, Legewie S, Herzel H, Westerhoff HV Kholodenko BN (2006) Effects of sequestration on signal transduction cascades. FEBS J 273, 895 906.
29. Salazar C Höfer T (2007) Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein-protein interactions. FEBS J 274, 1046 1061. (Pubitemid 46204423)
30. Kim SY Ferrell JE Jr. (2007) Substrate competition as a source of ultrasensitivity in the inactivation of Wee1. Cell 128, 1133 1145. (Pubitemid 46437260)
31. Ortega F, Garces JL, Mas F, Kholodenko BN Cascante M (2006) Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements. FEBS J 273, 3915 3926. (Pubitemid 44253648)
32. Cateau H Tanaka S (2002) Kinetic analysis of multisite phosphorylation using analytic solutions to Michaelis-Menten equations. J Theor Biol 217, 1 14.
33. Gunawardena J (2005) Multisite protein phosphorylation makes a good threshold but can be a poor switch. Proc Natl Acad Sci USA 102, 14617 14622. (Pubitemid 41457106)
34. Wang L Sontag ED (2008) On the number of steady states in a multiple futile cycle. J Math Biol 57, 29 52.
35. Gunawardena J (2007) Distributivity and processivity in multisite phosphorylation can be distinguished through steady-state invariants. Biophys J 93, 3828 3834. (Pubitemid 350223801)
36. Swain PS Siggia ED (2002) The role of proofreading in signal transduction specificity. Biophys J 82, 2928 2933. (Pubitemid 34547635)
37. McKeithan TW (1995) Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 92, 5042 5046.
38. Salazar C Höfer T (2003) Allosteric regulation of the transcription factor NFAT1 by multiple phosphorylation sites: a mathematical analysis. J Mol Biol 327, 31 45. (Pubitemid 36293301)
39. Salazar C Höfer T (2005) Activation of the transcription factor NFAT1: concerted or modular regulation? FEBS Lett 579, 621 626.
40. Klein P, Pawson T Tyers M (2003) Mathematical modeling suggests cooperative interactions between a disordered polyvalent ligand and a single receptor site. Curr Biol 13, 1669 1678. (Pubitemid 37216244)
41. Ferrell JE Jr. Bhatt RR (1997) Mechanistic studies of the dual phosphorylation of mitogen-activated protein kinase. J Biol Chem 272, 19008 19016. (Pubitemid 27318256)
42. Lenz P Swain PS (2006) An entropic mechanism to generate highly cooperative and specific binding from protein phosphorylations. Curr Biol 16, 2150 2155.
43. Borg M, Mittag T, Pawson T, Tyers M, Forman-Kay JD Chan HS (2007) Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity. Proc Natl Acad Sci USA 104, 9650 9655. (Pubitemid 47175321)
44. Yang L, MacLellan WR, Han Z, Weiss JN Qu Z (2004) Multisite phosphorylation and network dynamics of cyclin-dependent kinase signaling in the eukaryotic cell cycle. Biophys J 86, 3432 3443. (Pubitemid 38780228)
45. Goldbeter A (1995) A model for circadian oscillations in the Drosophila period protein (PER). Proc Biol Sci 261, 319 324.
46. Waas WF, Lo HH Dalby KN (2001) The kinetic mechanism of the dual phosphorylation of the ATF2 transcription factor by p38 mitogen-activated protein (MAP) kinase α. Implications for signal/response profiles of MAP kinase pathways. J Biol Chem 276, 5676 5684. (Pubitemid 37385717)
47. George AJ, Stark J Chan C (2005) Understanding specificity and sensitivity of T-cell recognition. Trends Immunol 26, 653 659. (Pubitemid 41628198)
48. Crabtree GR Olson EN (2002) NFAT signaling: choreographing the social lives of cells. Cell 109, S67 S79. (Pubitemid 34457853)
49. Hogan PG, Chen L, Nardone J Rao A (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 17, 2205 2232. (Pubitemid 37128637)
50. Gwack Y, Sharma S, Nardone J, Tanasa B, Iuga A, Srikanth S, Okamura H, Bolton D, Feske S, Hogan PG et al. (2006) A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature 441, 646 650. (Pubitemid 43927297)
51. Deshaies RJ Ferrell JE Jr. (2001) Multisite phosphorylation and the countdown to S phase. Cell 107, 819 822. (Pubitemid 34084972)
52. Orlicky S, Tang X, Willems A, Tyers M Sicheri F (2003) Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell 112, 243 256. (Pubitemid 36144113)
53. Rape M, Reddy SK Kirschner MW (2006) The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 124, 89 103. (Pubitemid 43069312)
54. Morton S, Davis RJ, McLaren A Cohen P (2003) A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. EMBO J 22, 3876 3886. (Pubitemid 36975714)
55. Gembitsky DS, Lawlor K, Jacovina A, Yaneva M Tempst P (2004) A prototype antibody microarray platform to monitor changes in protein tyrosine phosphorylation. Mol Cell Proteomics 3, 1102 1118. (Pubitemid 40012103)
56. Sachs K, Perez O, Pe'er D, Lauffenburger DA Nolan GP (2005) Causal protein-signaling networks derived from multiparameter single-cell data. Science 308, 523 529. (Pubitemid 40570578)
57. Ficarro SB, McCleland ML, Stukenberg PT, Burke DJ, Ross MM, Shabanowitz J, Hunt DF White FM (2002) Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 20, 301 305. (Pubitemid 34205425)
58. Selenko P, Frueh DP, Elsaesser SJ, Haas W, Gygi SP Wagner G (2008) In situ observation of protein phosphorylation by high-resolution NMR spectroscopy. Nat Struct Mol Biol 15, 321 329.
59. Byeon IJ, Li H, Song H, Gronenborn AM Tsai MD (2005) Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67. Nat Struct Mol Biol 12, 987 993.
60. Roach PJ (1991) Multisite and hierarchal protein phosphorylation. J Biol Chem 266, 14139 14142. (Pubitemid 21907470)
61. Fiol CJ, Wang A, Roeske RW Roach PJ (1990) Ordered multisite protein phosphorylation. Analysis of glycogen synthase kinase 3 action using model peptide substrates. J Biol Chem 265, 6061 6065. (Pubitemid 20148140)
62. Frame S, Cohen P Biondi RM (2001) A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell 7, 1321 1327. (Pubitemid 32607364)
63. Nolen B, Yun CY, Wong CF, McCammon JA, Fu XD Ghosh G (2001) The structure of Sky1p reveals a novel mechanism for constitutive activity. Nat Struct Biol 8, 176 183. (Pubitemid 32116072)
64. Ma CT, Velazquez-Dones A, Hagopian JC, Ghosh G, Fu XD Adams JA (2008) Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1. J Mol Biol 376, 55 68.
65. Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J He X (2005) A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438, 873 877. (Pubitemid 41753071)
66. Jia J, Tong C, Wang B, Luo L Jiang J (2004) Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature 432, 1045 1050. (Pubitemid 40052237)
67. Nishimura I, Yang Y Lu B (2004) PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116, 671 682. (Pubitemid 38326726)
68. Borgne A Meijer L (1996) Sequential dephosphorylation of p34(cdc2) on Thr-14 and Tyr-15 at the prophase/metaphase transition. J Biol Chem 271, 27847 27854. (Pubitemid 26367361)
69. Kennedy MJ, Lee KA, Niemi GA, Craven KB, Garwin GG, Saari JC Hurley JB (2001) Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation. Neuron 31, 87 101. (Pubitemid 32757091)
70. Burack WR Sturgill TW (1997) The activating dual phosphorylation of MAPK by MEK is nonprocessive. Biochemistry 36, 5929 5933. (Pubitemid 27257857)
71. Zhao Y Zhang ZY (2001) The mechanism of dephosphorylation of extracellular signal-regulated kinase 2 by mitogen-activated protein kinase phosphatase 3. J Biol Chem 276, 32382 32391. (Pubitemid 37384905)
72. Remenyi A, Good MC Lim WA (2006) Docking interactions in protein kinase and phosphatase networks. Curr Opin Struct Biol 16, 676 685.
73. Pellicena P Miller WT (2001) Processive phosphorylation of p130Cas by Scr depends on SH3-polyproline interactions. J Biol Chem 276, 28190 28196. (Pubitemid 37391523)
74. Mayer BJ, Hirai H Sakai R (1995) Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases. Curr Biol 5, 296 305.
75. Patwardhan P Miller WT (2007) Processive phosphorylation: mechanism and biological importance. Cell Signal 19, 2218 2226. (Pubitemid 47361682)
76. Jeffery DA, Springer M, King DS O'Shea EK (2001) Multi-site phosphorylation of Pho4 by the cyclin-CDK Pho80-Pho85 is semi-processive with site preference. J Mol Biol 306, 997 1010. (Pubitemid 33030001)
77. Bambara RA, Fay PJ Mallaber LM (1995) Methods of analyzing processivity. Methods Enzymol 262, 270 280.
78. Scott MP Miller WT (2000) A peptide model system for processive phosphorylation by Src family kinases. Biochemistry 39, 14531 14537.
79. Levchenko A, Bruck J Sternberg PW (2000) Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc Natl Acad Sci USA 97, 5818 5823. (Pubitemid 30367482)
80. Furdui CM, Lew ED, Schlessinger J Anderson KS (2006) Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol Cell 21, 711 717. (Pubitemid 43290737)
81. Patwardhan P, Shen Y, Goldberg GS Miller WT (2006) Individual Cas phosphorylation sites are dispensable for processive phosphorylation by Src and anchorage-independent cell growth. J Biol Chem 281, 20689 20697. (Pubitemid 44115411)
82. Salazar C Höfer T (2006) Kinetic models of phosphorylation cycles: a systematic approach using the rapid-equilibrium approximation for protein-protein interactions. Biosystems 83, 195 206. (Pubitemid 43199820)
83. Salazar C Höfer T (2006) Competition effects shape the response sensitivity and kinetics of phosphorylation cycles in cell signaling. Ann NY Acad Sci 1091, 517 530. (Pubitemid 47092263)
84. Tanoue T, Adachi M, Moriguchi T Nishida E (2000) A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol 2, 110 116.
85. Shen T, Zong C, Hamelberg D, McCammon JA Wolynes PG (2005) The folding energy landscape and phosphorylation: modelling the conformational switch of the NFAT regulatory domain. FASEB J 19, 1389 1395. (Pubitemid 41278997)
86. Volkman BF, Lipson D, Wemmer DE Kern D (2001) Two-state allosteric behavior in a single-domain signaling protein. Science 291, 2429 2433. (Pubitemid 32231808)
87. Velazquez-Dones A, Hagopian JC, Ma CT, Zhong XY, Zhou H, Ghosh G, Fu XD Adams JA (2005) Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty. J Biol Chem 280, 41761 41768. (Pubitemid 41832239)
88. Ngo JC, Chakrabarti S, Ding JH, Velazquez-Dones A, Nolen B, Aubol BE, Adams JA, Fu XD Ghosh G (2005) Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. Mol Cell 20, 77 89. (Pubitemid 41396564)
89. Shibasaki F, Price ER, Milan D McKeon F (1996) Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382, 370 373. (Pubitemid 26260467)
90. Al-Daraji WI, Grant KR, Ryan K, Saxton A Reynolds NJ (2002) Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporine A. J Invest Dermatol 118, 779 788. (Pubitemid 34526539)
91. Segel IH (1993) Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. Wiley-Intersciences, New York.
92. Cornish-Bowden A (2004) Fundamentals of Enzyme Kinetics, 3rd edn. Portland Press, London.
93. Tzafriri AR (2003) Michaelis-Menten kinetics at high enzyme concentrations. Bull Math Biol 65, 1111 1129. (Pubitemid 37446847)
94. Schnell S Maini PK (2000) Enzyme kinetics at high enzyme concentration. Bull Math Biol 62, 483 499.
95. Ciliberto A, Capuani F Tyson JJ (2007) Modeling networks of coupled enzymatic reactions using the total quasi-steady state approximation. PLoS Comput Biol 3, e45. (Pubitemid 46535738)
96. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK Weissman JS (2003) Global analysis of protein expression in yeast. Nature 425, 737 741. (Pubitemid 37314318)
97. Adams JA (2003) Activation loop phosphorylation and catalysis in protein kinases: is there functional evidence for the autoinhibitor model? Biochemistry 42, 601 607. (Pubitemid 36133283)
98. Goldbeter A Koshland DE Jr. (1981) An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci USA 78, 6840 6844. (Pubitemid 12216857)
99. LaPorte DC Koshland DE Jr. (1983) Phosphorylation of isocitrate dehydrogenase as a demonstration of enhanced sensitivity in covalent regulation. Nature 305, 286 290.
100. Meinke MH, Bishop JS Edstrom RD (1986) Zero-order ultrasensitivity in the regulation of glycogen phosphorylase. Proc Natl Acad Sci USA 83, 2865 2868. (Pubitemid 16041763)
101. Ortega F, Acerenza L, Westerhoff HV, Mas F Cascante M (2002) Product dependence and bifunctionality compromise the ultrasensitivity of signal transduction cascades. Proc Natl Acad Sci USA 99, 1170 1175. (Pubitemid 34136465)
102. Legewie S, Blüthgen N Herzel H (2005) Quantitative analysis of ultrasensitive responses. FEBS J 272, 4071 4079. (Pubitemid 41160915)
103. Edery I, Zwiebel LJ, Dembinska ME Rosbash M (1994) Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci USA 91, 2260 2264. (Pubitemid 24092083)
104. Welcker M, Singer J, Loeb KR, Grim J Bloecher A (2003) Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell 12, 381 392. (Pubitemid 37238925)
105. Kim SY, Song EJ, Lee KJ Ferrell JE Jr. (2005) Multisite M-phase phosphorylation of Xenopus Wee1A. Mol Cell Biol 25, 10580 10590. (Pubitemid 41681978)
106. Heinrich R, Neel BG Rapoport TA (2002) Mathematical models of protein kinase signal transduction. Mol Cell 9, 957 970. (Pubitemid 34626667)
107. Tanaka S, Tak YS Araki H (2007) The role of CDK in the initiation step of DNA replication in eukaryotes. Cell Div 2, 16. (Pubitemid 47019381)
108. Sheu YJ Stillman B (2006) Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell 24, 101 113. (Pubitemid 44466677)
109. Zegerman P Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445, 281 285. (Pubitemid 46122811)
110. 1 to S transition in Saccharomyces cerevisiae. Cell Cycle 7, 1391 1401.
111. Iakoucheva LM, Brown CJ, Lawson JD, Obradovic Z Dunker AK (2002) Intrinsic disorder in cell-signaling and cancer-associated proteins. J Mol Biol 323, 573 584. (Pubitemid 35283681)
112. Dyson HJ Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6, 197 208. (Pubitemid 40314921)
113. Verkhivker GM (2005) Protein conformational transitions coupled to binding in molecular recognition of unstructured proteins: deciphering the effect of intermolecular interactions on computational structure prediction of the p27Kip1 protein bound to the cyclin A-cyclin-dependent kinase 2 complex. Proteins 58, 706 716. (Pubitemid 40176042)
114. Gunasekaran K, Tsai CJ, Kumar S, Zanuy D Nussinov R (2003) Extended disordered proteins: targeting function with less scaffold. Trends Biochem Sci 28, 81 85. (Pubitemid 36165136)
115. Strickfaden SC, Winters MJ, Ben-Ari G, Lamson RE, Tyers M Pryciak PM (2007) A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway. Cell 128, 519 531. (Pubitemid 46198890)
116. Serber Z Ferrell JE Jr. (2007) Tuning bulk electrostatics to regulate protein function. Cell 128, 441 444. (Pubitemid 46198900)
117. Pufall MA, Lee GM, Nelson ML, Kang HS, Velyvis A, Kay LE, McIntosh LP Graves BJ (2005) Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science 309, 142 145. (Pubitemid 40934995)
118. Park KS, Mohapatra DP, Misonou H Trimmer JS (2006) Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science 313, 976 979. (Pubitemid 44267390)
119. Hlavacek WS, Redondo A, Wofsy C Goldstein B (2002) Kinetic proofreading in receptor-mediated transduction of cellular signals: receptor aggregation, partially activated receptors, and cytosolic messengers. Bull Math Biol 64, 887 911.
120. Torigoe C, Faeder JR, Oliver JM Goldstein B (2007) Kinetic proofreading of ligand-FcεRI interactions may persist beyond LAT phosphorylation. J Immunol 178, 3530 3535. (Pubitemid 46417618)
121. Hopfield JJ (1974) Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci USA 71, 4135 4139.
122. Cohen P (1992) Signal integration at the level of protein kinases, protein phosphatases and their substrates. Trends Biochem Sci 17, 408 413.
123. She QB, Solit DB, Ye Q, O'Reilly KE, Lobo J Rosen N (2005) The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells. Cancer Cell 8, 287 289. (Pubitemid 41443414)
124. Kitamura T, Kitamura Y, Kuroda S, Hino Y, Ando M, Kotani K, Konishi H, Matsuzaki H, Kikkawa U, Ogawa W et al. (1999) Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. Mol Cell Biol 19, 6286 6296. (Pubitemid 29399333)
125. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR III., Takemori H et al. (2004) The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119, 61 74. (Pubitemid 39349320)
126. Martinez-Quiles N, Ho HH, Kirschner MW, Ramesh N Geha RS (2004) Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Mol Cell Biol 24, 5269 5280. (Pubitemid 38738162)
127. Hübner A, Barrett T, Flavell RA Davis RJ (2008) Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol Cell 30, 415 425.
128. Rust MJ, Markson JS, Lane WS, Fisher DS O'Shea EK (2007) Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science 318, 809 812.
129. Bhaumik SR, Smith E Shilatifard A (2007) Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol 14, 1008 1016. (Pubitemid 350060343)
130. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X He X (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837 847. (Pubitemid 34327534)
131. Marin O, Bustos VH, Cesaro L, Meggio F, Pagano MA, Antonelli M, Allende CC, Pinna LA Allende JE (2003) A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins. Proc Natl Acad Sci USA 100, 10193 10200. (Pubitemid 37071855)
132. Duyster J, Baskaran R Wang JY (1995) Src homology 2 domain as a specificity determinant in the c Abl-mediated tyrosine phosphorylation of the RNA polymerase II carboxyl-terminal repeated domain. Proc Natl Acad Sci USA 92, 1555 1559.
133. Baskaran R, Chiang GG, Mysliwiec T, Kruh GD Wang JY (1997) Tyrosine phosphorylation of RNA polymerase II carboxyl-terminal domain by the Abl-related gene product. J Biol Chem 272, 18905 18909. (Pubitemid 27318242)