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Research Article

A Proline-Rich Sequence Unique to MEK1 and MEK2 Is Required for Raf Binding and Regulates MEK Function

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Pages 5214-5225 | Received 24 May 1995, Accepted 13 Jul 1995, Published online: 30 Mar 2023

REFERENCES

  • Alessi, D. R., Y. Saito, D. G. Campbell, P. Cohen, G. Sithanandam, U. Rapp, A. Ashworth, C. R. Marshall, and S. Cowley. 1994. Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1. EMBO J. 13:1610–1619.
  • Ambrosio, L., A. P. Mahowald, and N. Perrimon. 1989. Requirement of the Drosophila raf homologue for torso function. Nature (London) 342:288–291.
  • Anderson, N. G., J. L. Maller, N. K. Tonks, and T. W. Sturgill. 1990. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature (London) 343:651–653.
  • Boyle, W. J., P. van der Geer, and T. Hunter. 1991. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 201:110–149.
  • Brunet, A., G. Pages, and J. Pouyssegur. 1994. Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1). FEBS Lett. 346:299–303.
  • Burgering, B. M. T., A. M. M. de Vries-Smits, R. H. Medema, P. C. van Weeren, L. G. J. Tertoolen, and J. L. Bos. 1993. Epidermal growth factor induces phosphorylation of extracellular signal-regulated kinase 2 via multiple pathways. Mol. Cell. Biol. 13:7248–7256.
  • Catling, A. D., C. W. M. Reuter, M. E. Cox, S. J. Parsons, and M. J. Weber. 1994. Partial purification of a mitogen-activated protein kinase kinase activator from bovine brain. J. Biol. Chem. 269:30014–30021.
  • Cobb, M. H., D. J. Robbins, and T. G. Boulton. 1991. Extracellular signal-regulated kinases: ERKs in progress. Cell Regul. 2:965–978.
  • Cohen, G. B., R. Ren, and D. Baltimore. 1995. Modular binding domains in signal transducing proteins. Cell 80:237–248.
  • Cowley, S., H. Paterson, P. Kemp, and C. J. Marshall. 1994. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77:841–852.
  • Crews, C. M., A. Alessandrini, and R. L. Erikson. 1992. The primary structure of MEK, a protein that phosphorylates the ERK gene product. Science 258:478–480.
  • Crews, C. M., and R. L. Erikson. 1993. Extracellular signals and reversible protein phosphorylation: what to MEK of it all. Cell 74:215–217.
  • Davis, R. J. 1993. The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem. 20:14553–14556.
  • Dent, P., Y. H. Chow, J. Wu, D. K. Morrison, R. Jove, and T. W. Sturgill. 1994. Expression, purification and characterisation of recombinant mitogen-activated protein kinase kinases. Biochem. J. 303:105–112.
  • Dent, P., W. Haser, T. A. J. Haystead, L. A. Vincent, T. M. Roberts, and T. W. Sturgill. 1992. Activation of mitogen-activated protein kinase kinase by v-RAF in NIH 3T3 cells and in vitro. Science 257:1404–1407.
  • Der, C. J., T. Finkel, and G. M. Cooper. 1986. Biological and biochemical properties of human rasH genes mutated at codon 61. Cell 44:167–176.
  • Derijard, B., M. Hibi, I.-H. Wu, T. Barrett, B. Su, T. Deng, M. Karin, and R. J. Davis. 1994. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:1025–1037.
  • Derijard, B., J. Raingeaud, T. Barrett, I-H. Wu, J. Han, R. Ulevitch, and R. J. Davis. 1995. Independent human MAP kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267:682–685.
  • Dickson, B. F., Sprenger, D. Morrison, and E. Hafen. 1992. Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. Nature (London) 360:600–603.
  • Errede, B., and D. E. Levin. 1993. A conserved kinase cascade for MAP kinase activation in yeast. Curr. Opin. Cell Biol. 5:254–260.
  • Finney, R. E., S. M. Robbins, and J. M. Bishop. 1993. Association of pRAS and pRAF-1 in a complex correlates with activation of a signal transduction pathway. Curr. Biol. 3:805–812.
  • Force, T., J. V. Bonventre, G. Heidecker, U. Rapp, J. Avruch, and J. M. Kyriakis. 1994. Enzymatic characteristics of the c-Raf-1 protein kinase. Proc. Natl. Acad. Sci. USA 91:1270–1274.
  • Galcheva-Gargova, Z., B. Derijard, I.-H. Wu, and R. J. Davis. 1994. An osmosensing signal transduction pathway in mammalian cells. Science 265: 806–808.
  • Gomez, N., and P. Cohen. 1991. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature (London) 353: 170–173.
  • Han, J., J.-D. Lee, L. Bibbs, and R. J. Ulevitch. 1994. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265:808–811.
  • Han, M., A. Golden, Y. Han, and P. W. Sternberg. 1993. C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. Nature (London) 363:133–140.
  • Haystead, C. M. M., P. Gregory, A. Shirazi, P. Fadden, C. Mosse, P. Dent, and T. A. J. Haystead. 1994. Insulin activates a novel adipocyte mitogen-activated protein kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf. J. Biol. Chem. 269:12804–12808.
  • Heasley, L. E., and G. L. Johnson. 1992. The β PDGF receptor induces neuronal differentiation of PC12 cells. Mol. Biol. Cell 3:545–553.
  • Howe, L. R., S. J. Leevers, N. Gomez, S. Nakielny, P. Cohen, and C. J. Marshall. 1992. Activation of the MAP kinase pathway by the protein kinase RAF. Cell 71:335–342.
  • Huang, W., A. Alessandrini, C. M. Crews, and R. L. Erikson. 1993. Raf-1 forms a stable complex with MEK1 and activates MEK1 by serine phosphor-ylation. Proc. Natl. Acad. Sci. USA 90:10947–10951.
  • Huang, W., and R. L. Erikson. 1994. Constitutive activation of MEK1 by mutation of serine phosphorylation sites. Proc. Natl. Acad. Sci. USA 91: 8960–8963.
  • Hughes, D. A., A. Ashworth, and C. J. Marshall. 1993. Complementation of byr1 in fission yeast by mammalian MAP kinase kinase requires coexpression of Raf kinase. Nature (London) 364:349–352.
  • Jaiswal, R. K., S. A. Moodie, A. Wolfman, and G. E. Landreth. 1994. The mitogen-activated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras. Mol. Cell. Biol. 14:6944–6953.
  • Jelinek, T., A. D. Catling, C. W. M. Reuter, S. A. Moodie, A. Wolfman, and M. J. Weber. 1994. RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol. Cell. Biol. 14:8212–8218.
  • Kahan, C., K. Seuwen, S. Meloche, and J. Pouyssegur. 1992. Coordinate, biphasic activation of p44 mitogen-activated protein kinase and S6 kinase by growth factors in hamster fibroblasts. Evidence for thrombin-induced signals different from phosphoinositide turnover and adenylylcyclase inhibition. J. Biol. Chem. 267:13369–13375.
  • Kolch, W., G. Heidecker, P. Lloyd, and U. R. Rapp. 1991. Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Nature (London) 349:426–428.
  • Kyriakis, J. M., H. App, X. F. Zhang, P. Banerjee, D. L. Brautigan, U. R. Rapp, and J. Avruch. 1992. RAF-1 activates MAP kinase kinase. Nature (London) 358:417–421.
  • Kyriakis, J. M., P. Banerjee, E. Nikolakaki, T. Dai, E. A. Ruble, M. F. Ahmad, J. Avruch, and J. R. Woodgett. 1994. The stress-activated protein kinase subfamily of c-Jun kinases. Nature (London) 369:156–160.
  • Kyriakis, J. M., D. L. Brautigan, T. S. Ingebritsen, and J. Avruch. 1991. pp54 microtubule-associated protein-2 kinase requires both tyrosine and serine/ threonine phosphorylation for activity. J. Biol. Chem. 266:10043–10046.
  • Kyriakis, J. M., T. L. Force, U. R. Rapp, J. V. Bonventre, and J. Avruch. 1993. Mitogen-regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase kinase. J. Biol. Chem. 268:16009–16019.
  • Lange-Carter, C. A., C. M. Pleiman, A. M. Gardner, K. J. Blumer, and G. L. Johnson. 1993. A divergence in the MAP kinase regulatory network defined by MEK kinase and RAF. Science 260:315–319.
  • Leevers, S. J., H. Paterson, and C. J. Marshall. 1994. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature (London) 369:411–414.
  • Macdonald, S. G., C. M. Crews, L. Wu, J. Driller, R. Clark, R. L. Erikson, and F. McCormick. 1993. Reconstitution of the RAF-1–MEK–ERK signal transduction pathway in vitro. Mol. Cell. Biol. 13:6615–6620.
  • Mansour, S. J., W. T. Matten, A. S. Hermann, J. M. Candia, S. Rong, K. Fukasawa, G. F. Vande-Woude, and N. G. Ahn. 1994. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265: 966–970.
  • Mansour, S. J., K. A. Resing, J. M. Candi, A. S. Hermann, J. W. Gloor, K. R. Herskind, R. J. Davis, and N. G. Ahn. 1994. Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis. J. Biochem. 116:304–314.
  • Marshall, C. J. 1995. Specificity of receptor tyrosine kinase signalling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179–185.
  • Melnick, M. B., L. A. Perkins, M. Lee, L. Ambrosio, and N. Perrimon. 1993. Developmental and molecular characterization of mutations in the Drosoph-ila-raf serine/threonine protein kinase. Development 118:127–138.
  • Minden, A., A. Lin, M. McMahon, C. Lange-Carter, B. Derijard, R. Davis, G. L. Johnson, and M. Karin. 1994. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266:1719–1723.
  • Moodie, S. A., M. J. Paris, W. Kolch, and A. Wolfman. 1994. Association of MEK1 with p21ras ζ GMPPNP is dependent on B-Raf. Mol. Cell. Biol. 14: 7153–7162.
  • Moodie, S. A., B. M. Willumsen, M. J. Weber, and A. Wolfman. 1993. Complexes of RAS:GTP with RAF-1 and mitogen-activated protein kinase kinase. Science 260:1658–1661.
  • Neiman, A., B. J. Stevenson, H.-P. Xu, G. F. Sprague, Jr., I. Herskowitz, M. Wigler, and S. Marcus. 1993. Functional homology of the protein kinases required for sexual differentiation in Schizosaccharomyces pombe and Sac-charomyces cerevisiae suggests a conserved signal transduction module in eukaryotic organisms. Mol. Biol. Cell 4:107–120.
  • Nguyen, T. T., J.-C. Scimeca, C. Filloux, P. Peraldi, J.-L. Carpentier, and E. van Obberghen. 1993. Co-regulation of the mitogen-activated protein kinase, extracellular-regulated kinase-1 and the 90kDa ribosomal S6 kinase in PC12 cells. J. Biol. Chem. 268:9803–9810.
  • Osborne, W. R., R. A. Hock, M. Kaleko, and A. D. Miller. 1990. Long-term expression of human adenosine deaminase in mice after transplantation of bone marrow infected with amphotrophic retroviral vectors. Hum. Gene Ther. 1:31–41.
  • Pages, G., A. Brunet, G. L'Allemain, and J. Pouyssegur. 1994. Constitutive mutant and putative regulatory serine phosphorylation site of mammalian MAP kinase kinase (MEK1). EMBO J. 13:3003–3010.
  • Pang, L., C.-F. Zheng, K.-L. Guan, and A. R. Saltiel. 1995. Nerve growth factor stimulates a novel protein kinase in PC-12 cells that phosphorylates and activates mitogen-activated protein kinase kinase (MEK). Biochem. J., 307:513–519.
  • Payne, D. M., A. J. Rossomando, P. Martino, A. K. Erikson, J.-H. Her, J. Shabanowitz, D. F. Hunt, M. J. Weber, and T. W. Sturgill. 1991. Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J. 10:885–892.
  • Posada, J., N. Yew, N. G. Ahn, G. F. Vande Woude, and J. A. Cooper. 1993. Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro. Mol. Cell. Biol. 13:2546–2553.
  • Reuter, C. W. M., A. D. Catling, T. Jelinek, and M. J. Weber. 1995. Biochemical analysis of MEK activation in NIH3T3 fibroblasts. J. Biol. Chem. 270:7644–7655.
  • Rossomando, A. J., P. Dent, T. W. Sturgill, and D. R. Marshak. 1994. Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation. Mol. Cell. Biol. 14:1594–1602.
  • Rouse, J., P. Cohen, S. Trigon, M. Morange, A. Alonso-Llamazares, D. Zaminillo, T. Hunt, and A. R. Nebrada. 1994. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phos-phorylation of the small heat shock proteins. Cell 78:1027–1037.
  • Saito, Y., N. Gomez, D. G. Campbell, A. Ashworth, C. J. Marshall, and P. Cohen. 1994. The threonine residues in MAP kinase kinase 1 phosphorylated by MAP kinase in vitro are also phosphorylated in nerve growth factor-stimulated rat phaeochromocytoma (PC12) cells. FEBS Lett. 341:119–124.
  • Samuels, M. L., M. J. Weber, J. M. Bishop, and M. McMahon. 1993. Conditional transformation and rapid activation of the MAP kinase cascade by an estradiol-dependent human RAF-1 protein kinase. Mol. Cell. Biol. 13:6241–6252.
  • Sanchez, I., R. T. Hughes, B. J. Mayer, K. Yee, J. R. Woodgett, J. Avruch, J. M. Kyriakis, and L. I. Zon. 1994. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature (London) 372:794–798.
  • Schaap, D., J. van der Wal, L. R. Howe, C. J. Marshall, and W. J. van Blitterswijk. 1993. A dominant-negative mutant of raf blocks mitogen-activated kinase activation by growth factors and oncogenic p21ras. J. Biol. Chem. 268:20232–20236.
  • Stokoe, D., S. G. Macdonald, K. Cadwallader, M. Symons, and J. F. Hancock. 1994. Activation of Raf as a result of recruitment to the plasma membrane. Science 264:1463–1467.
  • Sturgill, T. W., and J. Wu. 1991. Recent progress in characterisation of protein kinase cascades for phosphorylation of ribosomal protein S6. Bio-chim. Biophys. Acta 1092:350–357.
  • Traverse, S., N. Gomez, H. Paterson, C. Marshall, and P. Cohen. 1992. Sustained activation of the mitogen-activated protein kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor. Biochem. J. 288:351–355.
  • Tsuda, L., Y. H. Inoue, M. Yoo, M. Mizuno, M. Hata, Y. Lim, T. Adachi-Yamada, H. Ryo, Y. Masamune, and Y. Nishida. 1993. A protein kinase similar to MAP kinase acts downstream of the Raf kinase in Drosophila. Cell 72:407–414.
  • Vaillancourt, R. R., A. M. Gardner, and G. L. Johnson. 1994. B-Raf-dependent regulation of the MEK-1/mitogen-activated protein kinase pathway in PC12 cells and regulation by cyclic AMP. Mol. Cell. Biol. 14:6522–6530.
  • Van Aelst, L., M. Barr, S. Marcus, A. Polverino, and M. Wigler. 1993. Complex formation between Ras and Raf and other protein kinases. Proc. Natl. Acad. Sci. USA 90:6213–6217.
  • Vojtek, A. B., S. M. Hollenberg, and J. A. Cooper. 1993. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74:205–214.
  • Warne, P. H., P. R. Viciana, and J. Downward. 1993. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro. Nature (London) 364:352–355.
  • Wu, J., J. K. Harrison, P. Dent, K. R. Lynch, M. J. Weber, and T. W. Sturgill. 1993. Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2. Mol. Cell. Biol. 8:4539–4548.
  • Wu, J., J. K. Harrison, L. A. Vincent, T. A. J. Haystead, H. Michel, D. F. Hunt, K. R. Lynch, and T. W. Sturgill. 1993. Molecular cloning of a protein-tyrosine/threonine kinase activating mitogen-activated protein (MAP) kinase: MAP kinase kinase. Proc. Natl. Acad. Sci. USA 90:173–177.
  • Yan, M., T. Dai, J. C. Deak, J. M. Kyriakis, L. I. Zon, J. R. Woodgett, and D. J. Templeton. 1994. Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature (London) 372:798–800.
  • Yan, M., and D. J. Templeton. 1994. Identification of 2 serine residues of MEK-1 that are differentially phosphorylated during activation by raf and MEK kinase. J. Biol. Chem. 269:19067–19073.
  • Zhang, X., J. Settleman, J. M. Kyriakis, E. Takeuchi-Suzuki, S. J. Elledge, M. S. Marshall, J. Bruder, U. R. Rapp, and J. Avruch. 1993. Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature (London) 364:308–313.
  • Zheng, C.-F., and K.-L. Guan. 1993. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J. Biol. Chem. 268:11435–11439.
  • Zheng, C.-F., and K.-L. Guan. 1994. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J. 13: 1123–1131.

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