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  • Original Paper
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The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain

Oncogene volume 19, pages 3894–3901 (2000)Cite this article

Abstract

Mutations of the tumor suppressor protein APC (Adenomatous Polyposis Coli) are linked to familiar and sporadic human colon cancer. Here we describe a novel interaction between the APC protein and the protein tyrosine phosphatase PTP-BL carrying five PDZ protein–protein interaction domains. Exclusively, the second PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-terminus of the APC protein, as determined by yeast two-hybrid studies. Using surface plasmon resonance analysis we established a dissociation constant (KD) of 8.1×10−9 M. We find that a naturally occurring splice insertion of five amino acids (PDZ2b) abolishes its binding affinity to the APC protein. The in vivo interaction between PTP-BL and the APC protein was shown by coprecipitation experiments in transfected COS cells. Furthermore, in cultured epithelial Madine Carnine Kidney cells the subcellular colocalization was demonstrated for the nucleus and also for the tips of cellular extensions. The interaction of the APC protein with a protein tyrosine phosphatase may indirectly modulate the steady state levels of tyrosine phosphorylations of associated proteins, such as β-catenin playing a major role in the regulation of cell division, migration and cell adhesion.

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References

  • Baeg GH, Matsumine A, Kuroda T, Bhattacharjee RN, Miyashiro I, Toyoshima K and Akiyama T. . 1995 EMBO J. 14: 5618–5625.

  • Banville D, Ahmad S, Stocco R and Shen SH. . 1994 J. Biol. Chem. 269: 22320–22327.

  • Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D and Birchmeier W. . 1998 Science 280: 596–599.

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R and Birchmeier W. . 1996 Nature 382: 638–642.

  • Chen C and Okayama H. . 1987 Mol. Cell Biol. 7: 2745–2752.

  • Cohen NA, Brenman JE, Snyder SH and Bredt DS. . 1996 Neuron 17: 759–767.

  • Cuppen E, Gerrits H, Pepers B, Wieringa B and Hendriks W. . 1998 Mol. Biol. Cell 9: 671–683.

  • Cuppen E, van Ham M, Pepers B, Wieringa B and Hendriks W. . 1999 FEBS Lett. 459: 291–298.

  • Deka J, Herter P, Sprenger-Haussels M, Koosch S, Franz D, Muller KM, Kuhnen C, Hoffmann I and Müller O. . 1999 Oncogene 18: 5654–5661.

  • Deka J, Kuhlmann J and Müller O. . 1998 Eur. J. Biochem. 253: 591–597.

  • Goold RG, Owen R and Gordon-Weeks PR. . 1999 J. Cell Sci. 112: 3373–3384.

  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L and Robertson M. . 1991 Cell 66: 589–600.

  • Hart MJ, de los S, Albert IN, Rubinfeld B and Polakis P. . 1998 Curr. Biol. 8: 573–581.

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW. . 1998 Science 281: 1509–1512.

  • Hendriks W, Schepens J, Bachner D, Rijss J, Zeeuwen P, Zechner U, Hameister H and Wieringa B. . 1995 J. Cell Biochem. 59: 418–430.

  • Hughes K, Nikolakaki E, Plyte SE, Totty NF and Woodgett JR. . 1993 EMBO J. 12: 803–808.

  • Ikeda S, Kishida M, Matsuura Y, Usui H and Kikuchi A. . 2000 Oncogene 19: 537–545.

  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S and Kikuchi A. . 1998 EMBO J. 17: 1371–1384.

  • Ishidate T, Matsumine A, Toyoshima K and Akiyama T. . 2000 Oncogene 19: 365–372.

  • Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA and Snyder SH. . 1998 Neuron 20: 115–124.

  • Joslyn G, Carlson M, Thliveris A, Albertsen H, Gelbert L, Samowitz W, Groden J, Stevens J, Spirio L and Robertson M. . 1991 Cell 66: 601–613.

  • Karlsson R and Falt A. . 1997 J. Immunol. Meth. 200: 121–133.

  • Kemler R. . 1993 Trends. Genet. 9: 317–321.

  • Kim E, DeMarco SJ, Marfatia SM, Chishti AH, Sheng M and Strehler EE. . 1998 J. Biol. Chem. 273: 1591–1595.

  • Kim L, Liu J and Kimmel AR. . 1999 Cell 99: 399–408.

  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P and McKechnie D. . 1991 Science 253: 661–665.

  • Kornau HC, Schenker LT, Kennedy MB and Seeburg PH. . 1995 Science 269: 1737–1740.

  • Kozlov G, Gehring K and Ekiel I. . 2000 Biochemistry 39: 2572–2580.

  • Maekawa K, Imagawa N, Nagamatsu M and Harada S. . 1994 FEBS Lett. 337: 200–206.

  • Marfatia SM, Morais-Cabral JH, Kim AC, Byron O and Chishti AH. . 1997 J. Biol. Chem. 272: 24191–24197.

  • Matsumine A, Ogai A, Senda T, Okumura N, Satoh K, Baeg GH, Kawahara T, Kobayashi S, Okada M, Toyoshima K and Akiyama T. . 1996 Science 272: 1020–1023.

  • Midgley CA, White S, Howitt R, Save V, Dunlop MG, Hall PA, Lane DP, Wyllie AH and Bubb VJ. . 1997 J. Pathol. 181: 426–433.

  • Miyashiro I, Senda T, Matsumine A, Baeg GH, Kuroda T, Shimano T, Miura S, Noda T, Kobayashi S and Monden M. . 1995 Oncogene 11: 89–96.

  • Morrison EE, Wardleworth BN, Askham JM, Markham AF and Meredith DM. . 1998 Oncogene 17: 3471–3477.

  • Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED and Garner CC. . 1996 Neuron 17: 255–265.

  • Müller T, Choidas A, Reichmann E and Ullrich A. . 1999 J. Biol. Chem. 274: 10173–10183.

  • Munemitsu S, Souza B, Müller O, Albert I, Rubinfeld B and Polakis P. . 1994 Cancer Res. 54: 3676–3681.

  • Murthy KK, Clark K, Fortin Y, Shen SH and Banville D. . 1999 J. Biol. Chem. 274: 20679–20687.

  • Näthke IS, Adams CL, Polakis P, Sellin JH and Nelson WJ. . 1996 J. Cell. Biol. 134: 165–179.

  • Neufeld KL and White RL. . 1997 Proc. Natl. Acad. Sci. USA 94: 3034–3039.

  • Niethammer M, Kim E and Sheng M. . 1996 J. Neurosci. 16: 2157–2163.

  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S and Hedge P. . 1991 Science 253: 665–669.

  • O'Shannessy DJ, Brigham-Burke M and Peck K. . 1992 Anal. Biochem. 205: 132–136.

  • Polakis P. . 1997 Biochim. Biophys. Acta. 1332: F127–F147.

  • Pollack AL, Barth AM, Altschuler Y, Nelson WJ and Mostov KE. . 1997 J. Cell. Biol. 137: 1651–1662.

  • Roura S, Miravet S, Piedra J, Garcia DH and Dunach M. . 1999 J. Biol. Chem. 274: 36734–36740.

  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S and Polakis P. . 1996 Science 272: 1023–1026.

  • Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain SH, Masiarz FR, Munemitsu S and Polakis P. . 1993 Science 262: 1731–1734.

  • Sakanaka C, Weiss JB and Williams LT. . 1998 Proc. Natl. Acad. Sci. USA 95: 3020–3023.

  • Saras J, Claesson-Welsh L, Heldin CH and Gonez LJ. . 1994 J. Biol. Chem. 269: 24082–24089.

  • Saras J, Franzen P, Aspenstrom P, Hellman U, Gonez LJ and Heldin CH. . 1997 J. Biol. Chem. 272: 24333–24338.

  • Sato T, Irie S, Kitada S and Reed JC. . 1995 Science 268: 411–415.

  • Seeling JM, Miller JR, Gil R, Moon RT, White R and Virshup DM. . 1999 Science 283: 2089–2091.

  • Songyang Z, Fanning AS, Fu C, Xu J, Marfatia SM, Chishti AH, Crompton A, Chan AC, Anderson JM and Cantley LC. . 1997 Science 275: 73–77.

  • Su LK, Burrell M, Hill DE, Gyuris J, Brent R, Wiltshire R, Trent J, Vogelstein B and Kinzler KW. . 1995 Cancer Res. 55: 2972–2977.

  • Su LK, Vogelstein B and Kinzler KW. . 1993 Science 262: 1734–1737.

  • Tseng HC, Lu Q, Henderson E and Graves DJ. . 1999 Proc. Natl. Acad. Sci. USA 96: 9503–9508.

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Acknowledgements

We thank Paul Polakis for providing the cDNA clone of human full-length APC gene. This work was supported by a grant from the Deutsche Forschungsgemeinschaft SFB452.

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Authors and Affiliations

  1. Department of Molecular Neurobiochemistry, Ruhr-University Bochum, 44780, Bochum, Germany

    Kai S Erdmann, Volkmar Lessmann, Lutz Herrmann, Volker Eulenburg & Rolf Heumann

  2. Arbeitsgruppe Biophysikalische Analytik, Max-Planck-Institut für molekulare Physiologie, 44227, Dortmund, Germany

    Jürgen Kuhlmann

  3. Arbeitsgruppe Tumorgenetik, Max-Planck-Institut für molekulare Physiologie, 44227, Dortmund, Germany

    Oliver Müller

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Erdmann, K., Kuhlmann, J., Lessmann, V. et al. The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Oncogene 19, 3894–3901 (2000). https://doi.org/10.1038/sj.onc.1203725

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