2f49 Citations

The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.

Science 311 822-6 (2006)
Related entries: 2f9g, 2fa2

Cited: 190 times
EuropePMC logo PMID: 16424299

Abstract

Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.

Reviews - 2f49 mentioned but not cited (3)

  1. Scaffold proteins: hubs for controlling the flow of cellular information. Good MC, Zalatan JG, Lim WA. Science 332 680-686 (2011)
  2. Substrate and docking interactions in serine/threonine protein kinases. Goldsmith EJ, Akella R, Min X, Zhou T, Humphreys JM. Chem Rev 107 5065-5081 (2007)
  3. Exploiting holistic approaches to model specificity in protein phosphorylation. Palmeri A, Ferrè F, Helmer-Citterich M. Front Genet 5 315 (2014)

Articles - 2f49 mentioned but not cited (4)

  1. Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK. Mace PD, Wallez Y, Egger MF, Dobaczewska MK, Robinson H, Pasquale EB, Riedl SJ. Nat Commun 4 1681 (2013)
  2. Engineering allosteric regulation in protein kinases. Pincus D, Pandey JP, Feder ZA, Creixell P, Resnekov O, Reynolds KA. Sci Signal 11 eaar3250 (2018)
  3. Hierarchical Organization Endows the Kinase Domain with Regulatory Plasticity. Creixell P, Pandey JP, Palmeri A, Bhattacharyya M, Creixell M, Ranganathan R, Pincus D, Yaffe MB. Cell Syst 7 371-383.e4 (2018)
  4. RNA Recognition-like Motifs Activate a Mitogen-Activated Protein Kinase. Phillips T, Tio CW, Omerza G, Rimal A, Lokareddy RK, Cingolani G, Winter E. Biochemistry 57 6878-6887 (2018)


Reviews citing this publication (47)

  1. Mechanisms of specificity in protein phosphorylation. Ubersax JA, Ferrell JE. Nat Rev Mol Cell Biol 8 530-541 (2007)
  2. Mitogen-activated protein kinase signaling in plants. Rodriguez MC, Petersen M, Mundy J. Annu Rev Plant Biol 61 621-649 (2010)
  3. Signalling ballet in space and time. Kholodenko BN, Hancock JF, Kolch W. Nat Rev Mol Cell Biol 11 414-426 (2010)
  4. Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Chen RE, Thorner J. Biochim Biophys Acta 1773 1311-1340 (2007)
  5. Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits. Bhattacharyya RP, Reményi A, Yeh BJ, Lim WA. Annu Rev Biochem 75 655-680 (2006)
  6. Protein dynamics and conformational disorder in molecular recognition. Mittag T, Kay LE, Forman-Kay JD. J Mol Recognit 23 105-116 (2010)
  7. Mitogen-activated protein kinase pathways and fungal pathogenesis. Zhao X, Mehrabi R, Xu JR. Eukaryot Cell 6 1701-1714 (2007)
  8. Cell Signaling and Stress Responses. Hotamisligil GS, Davis RJ. Cold Spring Harb Perspect Biol 8 a006072 (2016)
  9. The roles of MAPKs in disease. Lawrence MC, Jivan A, Shao C, Duan L, Goad D, Zaganjor E, Osborne J, McGlynn K, Stippec S, Earnest S, Chen W, Cobb MH. Cell Res 18 436-442 (2008)
  10. RNA templating the epigenome: long noncoding RNAs as molecular scaffolds. Spitale RC, Tsai MC, Chang HY. Epigenetics 6 539-543 (2011)
  11. Regulation of cross-talk in yeast MAPK signaling pathways. Saito H. Curr Opin Microbiol 13 677-683 (2010)
  12. Docking interactions in protein kinase and phosphatase networks. Reményi A, Good MC, Lim WA. Curr Opin Struct Biol 16 676-685 (2006)
  13. Fuzzy complexes: Specific binding without complete folding. Sharma R, Raduly Z, Miskei M, Fuxreiter M. FEBS Lett 589 2533-2542 (2015)
  14. Scaffolds: interaction platforms for cellular signalling circuits. Zeke A, Lukács M, Lim WA, Reményi A. Trends Cell Biol 19 364-374 (2009)
  15. Fuzziness: linking regulation to protein dynamics. Fuxreiter M. Mol Biosyst 8 168-177 (2012)
  16. Regulators and signalling in insect haemocyte immunity. Marmaras VJ, Lampropoulou M. Cell Signal 21 186-195 (2009)
  17. Pseudokinases-remnants of evolution or key allosteric regulators? Zeqiraj E, van Aalten DM. Curr Opin Struct Biol 20 772-781 (2010)
  18. Kinases and pseudokinases: lessons from RAF. Shaw AS, Kornev AP, Hu J, Ahuja LG, Taylor SS. Mol Cell Biol 34 1538-1546 (2014)
  19. Dynamic interactions of proteins in complex networks: a more structured view. Stein A, Pache RA, Bernadó P, Pons M, Aloy P. FEBS J 276 5390-5405 (2009)
  20. Protein-protein interactions in the allosteric regulation of protein kinases. Pellicena P, Kuriyan J. Curr Opin Struct Biol 16 702-709 (2006)
  21. Intrinsic disorder in cell signaling and gene transcription. Tantos A, Han KH, Tompa P. Mol Cell Endocrinol 348 457-465 (2012)
  22. Networks for the allosteric control of protein kinases. Shi Z, Resing KA, Ahn NG. Curr Opin Struct Biol 16 686-692 (2006)
  23. Lining the pockets of kinases and phosphatases. Gold MG, Barford D, Komander D. Curr Opin Struct Biol 16 693-701 (2006)
  24. Modularity and functional plasticity of scaffold proteins as p(l)acemakers in cell signaling. Pan CQ, Sudol M, Sheetz M, Low BC. Cell Signal 24 2143-2165 (2012)
  25. Protein networking: insights into global functional organization of proteomes. Pieroni E, de la Fuente van Bentem S, Mancosu G, Capobianco E, Hirt H, de la Fuente A. Proteomics 8 799-816 (2008)
  26. Seven-transmembrane receptor signalling and ERK compartmentalization. Caunt CJ, Finch AR, Sedgley KR, McArdle CA. Trends Endocrinol Metab 17 276-283 (2006)
  27. Interactions via intrinsically disordered regions: what kind of motifs? Pancsa R, Fuxreiter M. IUBMB Life 64 513-520 (2012)
  28. Mitogen-activated protein kinase signalling and ERK1/2 bistability in asthma. Alam R, Gorska MM. Clin Exp Allergy 41 149-159 (2011)
  29. Spatial and temporal signal processing and decision making by MAPK pathways. Atay O, Skotheim JM. J Cell Biol 216 317-330 (2017)
  30. p38 MAPK in cardioprotection - are we there yet? Martin ED, Bassi R, Marber MS. Br J Pharmacol 172 2101-2113 (2015)
  31. Modular approaches to expanding the functions of living matter. Chin JW. Nat Chem Biol 2 304-311 (2006)
  32. Synthetic biology: advancing biological frontiers by building synthetic systems. Chen YY, Galloway KE, Smolke CD. Genome Biol 13 240 (2012)
  33. Fuzziness and Frustration in the Energy Landscape of Protein Folding, Function, and Assembly. Gianni S, Freiberger MI, Jemth P, Ferreiro DU, Wolynes PG, Fuxreiter M. Acc Chem Res 54 1251-1259 (2021)
  34. Emerging complex pathways of the actomyosin powerstroke. Málnási-Csizmadia A, Kovács M. Trends Biochem Sci 35 684-690 (2010)
  35. Fine regulation of Saccharomyces cerevisiae MAPK pathways by post-translational modifications. Molina M, Cid VJ, Martín H. Yeast 27 503-511 (2010)
  36. Cellular Complexity in MAPK Signaling in Plants: Questions and Emerging Tools to Answer Them. Krysan PJ, Colcombet J. Front Plant Sci 9 1674 (2018)
  37. Computational insights for the discovery of non-ATP competitive inhibitors of MAP kinases. Schnieders MJ, Kaoud TS, Yan C, Dalby KN, Ren P. Curr Pharm Des 18 1173-1185 (2012)
  38. MAPK cell-cycle regulation in Saccharomyces cerevisiae and Candida albicans. Correia I, Alonso-Monge R, Pla J. Future Microbiol 5 1125-1141 (2010)
  39. Scaffolds are 'active' regulators of signaling modules. Alexa A, Varga J, Reményi A. FEBS J 277 4376-4382 (2010)
  40. Sexual attraction: on the role of fungal pheromone/receptor systems (A review). Kothe E. Acta Microbiol Immunol Hung 55 125-143 (2008)
  41. Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling. Manjunath GP, Ramanujam PL, Galande S. J Biosci 43 155-171 (2018)
  42. Dynamic New World: Refining Our View of Protein Structure, Function and Evolution. Mannige RV. Proteomes 2 128-153 (2014)
  43. Extreme Fuzziness: Direct Interactions between Two IDPs. Wang W, Wang D. Biomolecules 9 E81 (2019)
  44. Adaptability in protein structures: structural dynamics and implications in ligand design. Maity A, Majumdar S, Priya P, De P, Saha S, Ghosh Dastidar S. J Biomol Struct Dyn 33 298-321 (2015)
  45. Polyvalent design in the cGAS-STING pathway. Bennett ZT, Li S, Sumer BD, Gao J. Semin Immunol 56 101580 (2021)
  46. The molecular basis for cellular function of intrinsically disordered protein regions. Holehouse AS, Kragelund BB. Nat Rev Mol Cell Biol (2023)
  47. Specificity models in MAPK cascade signaling. Ma Y, Nicolet J. FEBS Open Bio 13 1177-1192 (2023)

Articles citing this publication (136)

  1. Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Tompa P, Fuxreiter M. Trends Biochem Sci 33 2-8 (2008)
  2. Systematic discovery of in vivo phosphorylation networks. Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jørgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalnikov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Russell RB, Bork P, Yaffe MB, Pawson T. Cell 129 1415-1426 (2007)
  3. Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. Chi A, Huttenhower C, Geer LY, Coon JJ, Syka JE, Bai DL, Shabanowitz J, Burke DJ, Troyanskaya OG, Hunt DF. Proc Natl Acad Sci U S A 104 2193-2198 (2007)
  4. Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Bashor CJ, Helman NC, Yan S, Lim WA. Science 319 1539-1543 (2008)
  5. A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway. Strickfaden SC, Winters MJ, Ben-Ari G, Lamson RE, Tyers M, Pryciak PM. Cell 128 519-531 (2007)
  6. The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Kannan N, Haste N, Taylor SS, Neuwald AF. Proc Natl Acad Sci U S A 104 1272-1277 (2007)
  7. Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. Maeder CI, Hink MA, Kinkhabwala A, Mayr R, Bastiaens PI, Knop M. Nat Cell Biol 9 1319-1326 (2007)
  8. Negative feedback that improves information transmission in yeast signalling. Yu RC, Pesce CG, Colman-Lerner A, Lok L, Pincus D, Serra E, Holl M, Benjamin K, Gordon A, Brent R. Nature 456 755-761 (2008)
  9. The scaffold protein Ste5 directly controls a switch-like mating decision in yeast. Malleshaiah MK, Shahrezaei V, Swain PS, Michnick SW. Nature 465 101-105 (2010)
  10. The Ste5 scaffold directs mating signaling by catalytically unlocking the Fus3 MAP kinase for activation. Good M, Tang G, Singleton J, Reményi A, Lim WA. Cell 136 1085-1097 (2009)
  11. Docking interactions induce exposure of activation loop in the MAP kinase ERK2. Zhou T, Sun L, Humphreys J, Goldsmith EJ. Structure 14 1011-1019 (2006)
  12. Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis. Ottmann C, Yasmin L, Weyand M, Veesenmeyer JL, Diaz MH, Palmer RH, Francis MS, Hauser AR, Wittinghofer A, Hallberg B. EMBO J 26 902-913 (2007)
  13. Substrate discrimination among mitogen-activated protein kinases through distinct docking sequence motifs. Sheridan DL, Kong Y, Parker SA, Dalby KN, Turk BE. J Biol Chem 283 19511-19520 (2008)
  14. Cross-talk and decision making in MAP kinase pathways. McClean MN, Mody A, Broach JR, Ramanathan S. Nat Genet 39 409-414 (2007)
  15. Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5. Hao N, Nayak S, Behar M, Shanks RH, Nagiec MJ, Errede B, Hasty J, Elston TC, Dohlman HG. Mol Cell 30 649-656 (2008)
  16. Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map. Wen Z, Wang Z, Wang S, Ravula R, Yang L, Xu J, Wang C, Zuo Z, Chow MS, Shi L, Huang Y. PLoS One 6 e18278 (2011)
  17. Mapping dynamic protein interactions in MAP kinase signaling using live-cell fluorescence fluctuation spectroscopy and imaging. Slaughter BD, Schwartz JW, Li R. Proc Natl Acad Sci U S A 104 20320-20325 (2007)
  18. Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. Pfander B, Diffley JF. EMBO J 30 4897-4907 (2011)
  19. Membrane localization of scaffold proteins promotes graded signaling in the yeast MAP kinase cascade. Takahashi S, Pryciak PM. Curr Biol 18 1184-1191 (2008)
  20. Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies. Richter C, West M, Odorizzi G. EMBO J 26 2454-2464 (2007)
  21. Dynamic scaffolding in a G protein-coupled signaling system. Mishra P, Socolich M, Wall MA, Graves J, Wang Z, Ranganathan R. Cell 131 80-92 (2007)
  22. Disentangling the complexity of mitogen-activated protein kinases and reactive oxygen species signaling. Pitzschke A, Hirt H. Plant Physiol 149 606-615 (2009)
  23. Structural disorder promotes assembly of protein complexes. Hegyi H, Schad E, Tompa P. BMC Struct Biol 7 65 (2007)
  24. Alteration of substrate specificity: the variable N-terminal domain of tobacco Ca(2+)-dependent protein kinase is important for substrate recognition. Ito T, Nakata M, Fukazawa J, Ishida S, Takahashi Y. Plant Cell 22 1592-1604 (2010)
  25. Mechanism and consequence of the autoactivation of p38α mitogen-activated protein kinase promoted by TAB1. DeNicola GF, Martin ED, Chaikuad A, Bassi R, Clark J, Martino L, Verma S, Sicard P, Tata R, Atkinson RA, Knapp S, Conte MR, Marber MS. Nat Struct Mol Biol 20 1182-1190 (2013)
  26. How scaffolds shape MAPK signaling: what we know and opportunities for systems approaches. Witzel F, Maddison L, Blüthgen N. Front Physiol 3 475 (2012)
  27. Computational modeling of cellular signaling processes embedded into dynamic spatial contexts. Angermann BR, Klauschen F, Garcia AD, Prustel T, Zhang F, Germain RN, Meier-Schellersheim M. Nat Methods 9 283-289 (2012)
  28. RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex. Tang H, Park S, Sun SC, Trumbly R, Ren G, Tsung E, Yeung KC. FEBS Lett 584 662-668 (2010)
  29. A highly conserved MAPK-docking site in Mst7 is essential for Pmk1 activation in Magnaporthe grisea. Zhao X, Xu JR. Mol Microbiol 63 881-894 (2007)
  30. Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases. Ho DT, Bardwell AJ, Grewal S, Iverson C, Bardwell L. J Biol Chem 281 13169-13179 (2006)
  31. Scaffold proteins confer diverse regulatory properties to protein kinase cascades. Locasale JW, Shaw AS, Chakraborty AK. Proc Natl Acad Sci U S A 104 13307-13312 (2007)
  32. High levels of structural disorder in scaffold proteins as exemplified by a novel neuronal protein, CASK-interactive protein1. Balázs A, Csizmok V, Buday L, Rakács M, Kiss R, Bokor M, Udupa R, Tompa K, Tompa P. FEBS J 276 3744-3756 (2009)
  33. A novel actin binding site of myosin required for effective muscle contraction. Várkuti BH, Yang Z, Kintses B, Erdélyi P, Bárdos-Nagy I, Kovács AL, Hári P, Kellermayer M, Vellai T, Málnási-Csizmadia A. Nat Struct Mol Biol 19 299-306 (2012)
  34. Unmasking determinants of specificity in the human kinome. Creixell P, Palmeri A, Miller CJ, Lou HJ, Santini CC, Nielsen M, Turk BE, Linding R. Cell 163 187-201 (2015)
  35. HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa. Jonkers W, Leeder AC, Ansong C, Wang Y, Yang F, Starr TL, Camp DG, Smith RD, Glass NL. PLoS Genet 10 e1004783 (2014)
  36. Cyclin-specific docking motifs promote phosphorylation of yeast signaling proteins by G1/S Cdk complexes. Bhaduri S, Pryciak PM. Curr Biol 21 1615-1623 (2011)
  37. The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions. Ritterhoff S, Farah CM, Grabitzki J, Lochnit G, Skurat AV, Schmitz ML. EMBO J 29 3750-3761 (2010)
  38. Engineering robust control of two-component system phosphotransfer using modular scaffolds. Whitaker WR, Davis SA, Arkin AP, Dueber JE. Proc Natl Acad Sci U S A 109 18090-18095 (2012)
  39. Dose-to-duration encoding and signaling beyond saturation in intracellular signaling networks. Behar M, Hao N, Dohlman HG, Elston TC. PLoS Comput Biol 4 e1000197 (2008)
  40. Multiple WASP-interacting protein recognition motifs are required for a functional interaction with N-WASP. Peterson FC, Deng Q, Zettl M, Prehoda KE, Lim WA, Way M, Volkman BF. J Biol Chem 282 8446-8453 (2007)
  41. The surprising dynamics of scaffolding proteins. Garbett D, Bretscher A. Mol Biol Cell 25 2315-2319 (2014)
  42. Exploitation of latent allostery enables the evolution of new modes of MAP kinase regulation. Coyle SM, Flores J, Lim WA. Cell 154 875-887 (2013)
  43. Quantitative effect of scaffold abundance on signal propagation. Chapman SA, Asthagiri AR. Mol Syst Biol 5 313 (2009)
  44. Arrestin-3 binds c-Jun N-terminal kinase 1 (JNK1) and JNK2 and facilitates the activation of these ubiquitous JNK isoforms in cells via scaffolding. Kook S, Zhan X, Kaoud TS, Dalby KN, Gurevich VV, Gurevich EV. J Biol Chem 288 37332-37342 (2013)
  45. Letter Modularity of MAP kinases allows deformation of their signalling pathways. Mody A, Weiner J, Ramanathan S. Nat Cell Biol 11 484-491 (2009)
  46. JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases. Zhan X, Kaoud TS, Kook S, Dalby KN, Gurevich VV. J Biol Chem 288 28535-28547 (2013)
  47. Nucleus-specific and cell cycle-regulated degradation of mitogen-activated protein kinase scaffold protein Ste5 contributes to the control of signaling competence. Garrenton LS, Braunwarth A, Irniger S, Hurt E, Künzler M, Thorner J. Mol Cell Biol 29 582-601 (2009)
  48. Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells. Richardson L, Dixon CL, Aguilera-Aguirre L, Menon R. Biol Reprod 99 1100-1112 (2018)
  49. The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2. Hendus-Altenburger R, Pedraz-Cuesta E, Olesen CW, Papaleo E, Schnell JA, Hopper JT, Robinson CV, Pedersen SF, Kragelund BB. BMC Biol 14 31 (2016)
  50. Distal recognition sites in substrates are required for efficient phosphorylation by the cAMP-dependent protein kinase. Deminoff SJ, Ramachandran V, Herman PK. Genetics 182 529-539 (2009)
  51. Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase. Won AP, Garbarino JE, Lim WA. Proc Natl Acad Sci U S A 108 9809-9814 (2011)
  52. WNK1 is a novel regulator of Munc18c-syntaxin 4 complex formation in soluble NSF attachment protein receptor (SNARE)-mediated vesicle exocytosis. Oh E, Heise CJ, English JM, Cobb MH, Thurmond DC. J Biol Chem 282 32613-32622 (2007)
  53. Counteractive control of polarized morphogenesis during mating by mitogen-activated protein kinase Fus3 and G1 cyclin-dependent kinase. Yu L, Qi M, Sheff MA, Elion EA. Mol Biol Cell 19 1739-1752 (2008)
  54. Solution NMR insights into docking interactions involving inactive ERK2. Piserchio A, Warthaka M, Devkota AK, Kaoud TS, Lee S, Abramczyk O, Ren P, Dalby KN, Ghose R. Biochemistry 50 3660-3672 (2011)
  55. Evolutionary reshaping of fungal mating pathway scaffold proteins. Côte P, Sulea T, Dignard D, Wu C, Whiteway M. mBio 2 e00230-10 (2011)
  56. Machines vs. ensembles: effective MAPK signaling through heterogeneous sets of protein complexes. Suderman R, Deeds EJ. PLoS Comput Biol 9 e1003278 (2013)
  57. Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module. Glatz G, Gógl G, Alexa A, Reményi A. J Biol Chem 288 8596-8609 (2013)
  58. Resting and active states of the ERK2:HePTP complex. Francis DM, Różycki B, Tortajada A, Hummer G, Peti W, Page R. J Am Chem Soc 133 17138-17141 (2011)
  59. SR protein kinase 1 is resilient to inactivation. Ngo JC, Gullingsrud J, Giang K, Yeh MJ, Fu XD, Adams JA, McCammon JA, Ghosh G. Structure 15 123-133 (2007)
  60. Src family kinases directly regulate JIP1 module dynamics and activation. Nihalani D, Wong H, Verma R, Holzman LB. Mol Cell Biol 27 2431-2441 (2007)
  61. Understanding the specificity of a docking interaction between JNK1 and the scaffolding protein JIP1. Yan C, Kaoud T, Lee S, Dalby KN, Ren P. J Phys Chem B 115 1491-1502 (2011)
  62. Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli. Suen KM, Lin CC, George R, Melo FA, Biggs ER, Ahmed Z, Drake MN, Arur S, Arold ST, Ladbury JE. Nat Struct Mol Biol 20 620-627 (2013)
  63. Scaffold Function of Ca2+-Dependent Protein Kinase: Tobacco Ca2+-DEPENDENT PROTEIN KINASE1 Transfers 14-3-3 to the Substrate REPRESSION OF SHOOT GROWTH after Phosphorylation. Ito T, Nakata M, Fukazawa J, Ishida S, Takahashi Y. Plant Physiol 165 1737-1750 (2014)
  64. Spatial control of Shoc2-scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5. Jang ER, Jang H, Shi P, Popa G, Jeoung M, Galperin E. J Cell Sci 128 4428-4441 (2015)
  65. CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5. Repetto MV, Winters MJ, Bush A, Reiter W, Hollenstein DM, Ammerer G, Pryciak PM, Colman-Lerner A. Mol Cell 69 938-952.e6 (2018)
  66. Molecular imaging of c-Met tyrosine kinase activity. Zhang L, Virani S, Zhang Y, Bhojani MS, Burgess TL, Coxon A, Galban CJ, Ross BD, Rehemtulla A. Anal Biochem 412 1-8 (2011)
  67. Simple synthetic protein scaffolds can create adjustable artificial MAPK circuits in yeast and mammalian cells. Ryu J, Park SH. Sci Signal 8 ra66 (2015)
  68. The role of Candida albicans FAR1 in regulation of pheromone-mediated mating, gene expression and cell cycle arrest. Côte P, Whiteway M. Mol Microbiol 68 392-404 (2008)
  69. Activation of the Smk1 mitogen-activated protein kinase by developmentally regulated autophosphorylation. Whinston E, Omerza G, Singh A, Tio CW, Winter E. Mol Cell Biol 33 688-700 (2013)
  70. Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs. Kostenko EV, Olabisi OO, Sahay S, Rodriguez PL, Whitehead IP. Mol Cell Biol 26 8964-8975 (2006)
  71. Heterogeneous Tau-Tubulin Complexes Accelerate Microtubule Polymerization. Li XH, Rhoades E. Biophys J 112 2567-2574 (2017)
  72. Selective regulation of MAP kinase signaling by an endomembrane phosphatidylinositol 4-kinase. Cappell SD, Dohlman HG. J Biol Chem 286 14852-14860 (2011)
  73. Membrane recruitment of scaffold proteins drives specific signaling. Pincet F. PLoS One 2 e977 (2007)
  74. Knockdown of Sec8 enhances the binding affinity of c-Jun N-terminal kinase (JNK)-interacting protein 4 for mitogen-activated protein kinase kinase 4 (MKK4) and suppresses the phosphorylation of MKK4, p38, and JNK, thereby inhibiting apoptosis. Tanaka T, Iino M, Goto K. FEBS J 281 5237-5250 (2014)
  75. Regulation of signal duration and the statistical dynamics of kinase activation by scaffold proteins. Locasale JW, Chakraborty AK. PLoS Comput Biol 4 e1000099 (2008)
  76. Signal inhibition by a dynamically regulated pool of monophosphorylated MAPK. Nagiec MJ, McCarter PC, Kelley JB, Dixit G, Elston TC, Dohlman HG. Mol Biol Cell 26 3359-3371 (2015)
  77. Distinct docking mechanisms mediate interactions between the Msg5 phosphatase and mating or cell integrity mitogen-activated protein kinases (MAPKs) in Saccharomyces cerevisiae. Palacios L, Dickinson RJ, Sacristán-Reviriego A, Didmon MP, Marín MJ, Martín H, Keyse SM, Molina M. J Biol Chem 286 42037-42050 (2011)
  78. Expression profiling identifies epoxy anthraquinone derivative as a DNA topoisomerase inhibitor. Gheeya J, Johansson P, Chen QR, Dexheimer T, Metaferia B, Song YK, Wei JS, He J, Pommier Y, Khan J. Cancer Lett 293 124-131 (2010)
  79. In vivo characterization of the scaffold activity of flotillin on the membrane kinase KinC of Bacillus subtilis. Schneider J, Mielich-Süss B, Böhme R, Lopez D. Microbiology (Reading) 161 1871-1887 (2015)
  80. Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast. Choudhury S, Baradaran-Mashinchi P, Torres MP. Cell Rep 23 1504-1515 (2018)
  81. The HamE scaffold positively regulates MpkB phosphorylation to promote development and secondary metabolism in Aspergillus nidulans. Frawley D, Karahoda B, Sarikaya Bayram Ö, Bayram Ö. Sci Rep 8 16588 (2018)
  82. The WW domain of the scaffolding protein IQGAP1 is neither necessary nor sufficient for binding to the MAPKs ERK1 and ERK2. Bardwell AJ, Lagunes L, Zebarjedi R, Bardwell L. J Biol Chem 292 8750-8761 (2017)
  83. Ultrasensitivity in phosphorylation-dephosphorylation cycles with little substrate. Martins BM, Swain PS. PLoS Comput Biol 9 e1003175 (2013)
  84. Autophosphorylation of the Smk1 MAPK is spatially and temporally regulated by Ssp2 during meiotic development in yeast. Tio CW, Omerza G, Sunder S, Winter E. Mol Biol Cell 26 3546-3555 (2015)
  85. Co-conserved MAPK features couple D-domain docking groove to distal allosteric sites via the C-terminal flanking tail. Nguyen T, Ruan Z, Oruganty K, Kannan N. PLoS One 10 e0119636 (2015)
  86. Differential Role of Threonine and Tyrosine Phosphorylation in the Activation and Activity of the Yeast MAPK Slt2. González-Rubio G, Sellers-Moya Á, Martín H, Molina M. Int J Mol Sci 22 1110 (2021)
  87. Dynamic ubiquitination of the mitogen-activated protein kinase kinase (MAPKK) Ste7 determines mitogen-activated protein kinase (MAPK) specificity. Hurst JH, Dohlman HG. J Biol Chem 288 18660-18671 (2013)
  88. Quantitative measurement of protein relocalization in live cells. Bush A, Colman-Lerner A. Biophys J 104 727-736 (2013)
  89. Switch-like Transitions Insulate Network Motifs to Modularize Biological Networks. Atay O, Doncic A, Skotheim JM. Cell Syst 3 121-132 (2016)
  90. Enzyme Sequestration as a Tuning Point in Controlling Response Dynamics of Signalling Networks. Feng S, Ollivier JF, Soyer OS. PLoS Comput Biol 12 e1004918 (2016)
  91. Reassembly of JIP1 scaffold complex in JNK MAP kinase pathway using heterologous protein interactions. Moon J, Park SH. PLoS One 9 e96797 (2014)
  92. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction. Hu J, Neiswinger J, Zhang J, Zhu H, Qian J. PLoS Comput Biol 11 e1004508 (2015)
  93. The kinase domain of CK1 enzymes contains the localization cue essential for compartmentalized signaling at the spindle pole. Elmore ZC, Guillen RX, Gould KL. Mol Biol Cell 29 1664-1674 (2018)
  94. How can yeast cells decide between three activated MAP kinase pathways? A model approach. Rensing L, Ruoff P. J Theor Biol 257 578-587 (2009)
  95. Quantitative analysis of the yeast pheromone pathway. Shellhammer JP, Pomeroy AE, Li Y, Dujmusic L, Elston TC, Hao N, Dohlman HG. Yeast 36 495-518 (2019)
  96. The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules. De Nicola GF, Bassi R, Nichols C, Fernandez-Caggiano M, Golforoush PA, Thapa D, Anderson R, Martin ED, Verma S, Kleinjung J, Laing A, Hutchinson JP, Eaton P, Clark J, Marber MS. JCI Insight 3 121144 (2018)
  97. C-terminal Ser/Thr residues are vital for the regulatory role of Ste7 in the asexual cycle and virulence of Beauveria bassiana. Wang ZK, Cai Q, Tong SM, Ying SH, Feng MG. Appl Microbiol Biotechnol 102 6973-6986 (2018)
  98. Mechanistic studies of the autoactivation of PAK2: a two-step model of cis initiation followed by trans amplification. Wang J, Wu JW, Wang ZX. J Biol Chem 286 2689-2695 (2011)
  99. Functions for Cdc42p BEM adaptors in regulating a differentiation-type MAP kinase pathway. Basu S, González B, Li B, Kimble G, Kozminski KG, Cullen PJ. Mol Biol Cell 31 491-510 (2020)
  100. How MAP kinase modules function as robust, yet adaptable, circuits. Tian T, Harding A. Cell Cycle 13 2379-2390 (2014)
  101. Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator. Ordyan M, Bartol T, Kennedy M, Rangamani P, Sejnowski T. PLoS Comput Biol 16 e1008015 (2020)
  102. Proper protein glycosylation promotes mitogen-activated protein kinase signal fidelity. Lien EC, Nagiec MJ, Dohlman HG. Biochemistry 52 115-124 (2013)
  103. Core signalling motif displaying multistability through multi-state enzymes. Feng S, Sáez M, Wiuf C, Feliu E, Soyer OS. J R Soc Interface 13 20160524 (2016)
  104. Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination. Groves B, Khakhar A, Nadel CM, Gardner RG, Seelig G. Elife 5 e15200 (2016)
  105. ScaPD: a database for human scaffold proteins. Han X, Wang J, Wang J, Liu S, Hu J, Zhu H, Qian J. BMC Bioinformatics 18 386 (2017)
  106. Systematic analysis of F-box proteins reveals a new branch of the yeast mating pathway. Rangarajan N, Gordy CL, Askew L, Bevill SM, Elston TC, Errede B, Hurst JH, Kelley JB, Sheetz JB, Suzuki SK, Valentin NH, Young E, Dohlman HG. J Biol Chem 294 14717-14731 (2019)
  107. The Relationship between Effective Molarity and Affinity Governs Rate Enhancements in Tethered Kinase-Substrate Reactions. Speltz EB, Zalatan JG. Biochemistry 59 2182-2193 (2020)
  108. Mitogen-activated protein kinases, Fus3 and Kss1, regulate chronological lifespan in yeast. Aluru M, McKinney T, Venero AL, Choudhury S, Torres M. Aging (Albany NY) 9 2587-2609 (2017)
  109. Comment Shaping specificity in signaling networks. Albert R, Oltvai ZN. Nat Genet 39 286-287 (2007)
  110. Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase. Tio CW, Omerza G, Phillips T, Lou HJ, Turk BE, Winter E. Mol Cell Biol 37 e00607-16 (2017)
  111. Symmetry breaking: scaffold plays matchmaker for polarity signaling proteins. Atkins BD, Yoshida S, Pellman D. Curr Biol 18 R1130-2 (2008)
  112. FBP21's C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase. Sticht J, Bertazzon M, Henning LM, Licha JR, Abualrous ET, Freund C. Biophys J 116 406-418 (2019)
  113. MAPK modulation of yeast pheromone signaling output and the role of phosphorylation sites in the scaffold protein Ste5. Winters MJ, Pryciak PM. Mol Biol Cell 30 1037-1049 (2019)
  114. Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5. van Drogen F, Mishra R, Rudolf F, Walczak MJ, Lee SS, Reiter W, Hegemann B, Pelet S, Dohnal I, Binolfi A, Yudina Z, Selenko P, Wider G, Ammerer G, Peter M. J Cell Biol 218 3117-3133 (2019)
  115. The RING domain of the scaffold protein Ste5 adopts a molten globular character with high thermal and chemical stability. Walczak MJ, Samatanga B, van Drogen F, Peter M, Jelesarov I, Wider G. Angew Chem Int Ed Engl 53 1320-1323 (2014)
  116. A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast. Jamalzadeh S, Pujari AN, Cullen PJ. Sci Rep 10 22184 (2020)
  117. A time-resolved interaction analysis of Bem1 reconstructs the flow of Cdc42 during polar growth. Grinhagens S, Dünkler A, Wu Y, Rieger L, Brenner P, Gronemeyer T, Mulaw MA, Johnsson N. Life Sci Alliance 3 e202000813 (2020)
  118. New connections, new components, real dynamics. Bader JS. Sci Signal 2 pe48 (2009)
  119. Optimal ratio of scaffold complex to free Fus3 to maximise the accumulation of phosphorylated Fus3 in yeast pheromone signalling pathway. Nakabayashi J. IET Syst Biol 6 9-21 (2012)
  120. Patterning Microtubule Network Organization Reshapes Cell-Like Compartments. Bermudez JG, Deiters A, Good MC. ACS Synth Biol 10 1338-1350 (2021)
  121. Regulation of the activity of the bacterial histidine kinase PleC by the scaffolding protein PodJ. Zhang C, Zhao W, Duvall SW, Kowallis KA, Childers WS. J Biol Chem 298 101683 (2022)
  122. Regulatory basis for reproductive flexibility in a meningitis-causing fungal pathogen. Hu P, Ding H, Liu H, Yang Y, Chen L, He GJ, Ke W, Zhu P, Tian X, Peng Y, Shen Z, Yao X, Tao C, Yang E, Liao G, Liu X, Wang L. Nat Commun 13 7938 (2022)
  123. Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling. Pesce CG, Zdraljevic S, Peria WJ, Bush A, Repetto MV, Rockwell D, Yu RC, Colman-Lerner A, Brent R. Mol Syst Biol 14 e7390 (2018)
  124. The optimal docking strength for reversibly tethered kinases. Dyla M, González Foutel NS, Otzen DE, Kjaergaard M. Proc Natl Acad Sci U S A 119 e2203098119 (2022)
  125. Cell biology. A scaffold switch to insulate. Davis RJ. Science 337 1178-1179 (2012)
  126. Combinatorial phosphorylation modulates the structure and function of the G protein γ subunit in yeast. Nassiri Toosi Z, Su X, Austin R, Choudhury S, Li W, Pang YT, Gumbart JC, Torres MP. Sci Signal 14 eabd2464 (2021)
  127. Mapping regions in Ste5 that support Msn5-dependent and -independent nuclear export. Hu Z, Wang Y, Yu L, Mahanty SK, Mendoza N, Elion EA. Biochem Cell Biol 94 109-128 (2016)
  128. Three-state kinetic mechanism for scaffold-mediated signal transduction. Locasale JW. Phys Rev E Stat Nonlin Soft Matter Phys 78 051921 (2008)
  129. Correlation Between Improved Mating Efficiency and Weakened Scaffold-Kinase Interaction in the Mating Pheromone Response Pathway Revealed by Interspecies Complementation. Shi T, Zeng J, Zhou J, Yu Y, Lu H. Front Microbiol 13 865829 (2022)
  130. Effects of HSP70 chaperones Ssa1 and Ssa2 on Ste5 scaffold and the mating mitogen-activated protein kinase (MAPK) pathway in Saccharomyces cerevisiae. Farley FW, McCully RR, Maslo PB, Yu L, Sheff MA, Sadeghi H, Elion EA. PLoS One 18 e0289339 (2023)
  131. Functional Properties of the MAP Kinase UeKpp2 in Ustilago esculenta. Zhang Y, Hu Y, Cao Q, Yin Y, Xia W, Cui H, Yu X, Ye Z. Front Microbiol 11 1053 (2020)
  132. Global quantitative understanding of non-equilibrium cell fate decision-making in response to pheromone. Li S, Liu Q, Wang E, Wang J. iScience 26 107885 (2023)
  133. Isc10, an inhibitor of the Smk1 MAPK, prevents activation loop autophosphorylation and substrate phosphorylation through separate mechanisms. Rimal A, Swayne TM, Kamdar ZP, Tewey MA, Winter E. J Biol Chem 298 102450 (2022)
  134. Mechanism of commitment to a mating partner in Saccharomyces cerevisiae. Jacobs KC, Gorman O, Lew DJ. Mol Biol Cell 33 ar112 (2022)
  135. Congress Science amongst the vines. Meeting on signalling systems. Pitson SM, Goodall GJ, Guthridge MA. EMBO Rep 9 425-428 (2008)
  136. Signal transduction at GPCRs: Allosteric activation of the ERK MAPK by β-arrestin. Kahsai AW, Shah KS, Shim PJ, Lee MA, Shreiber BN, Schwalb AM, Zhang X, Kwon HY, Huang LY, Soderblom EJ, Ahn S, Lefkowitz RJ. Proc Natl Acad Sci U S A 120 e2303794120 (2023)