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The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion

Oncogene volume 22, pages 4175–4185 (2003)Cite this article

Abstract

Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated platelet-derived growth factor (PDGF) β-receptor in a site-selective manner (Kovalenko et al. (2000). J. Biol. Chem. 275, 16219–16226). We analysed cell lines with inducible DEP-1 expression for cellular functions of DEP-1. Several aspects of PDGFβ-receptor signaling were negatively affected by DEP-1 expression. These include PDGF-stimulated activation of inositol trisphosphate formation, Erk1/2, p21Ras, and Src. Activation of receptor-associated phosphoinositide-3 kinase activity and of Akt/PKB were weakly attenuated at early time points of stimulation. Inhibition of PDGF-stimulated signaling depended on DEP-1 catalytic activity. Importantly, DEP-1 inhibited PDGF-stimulated cell migration. The catalytically inactive DEP-1 C1239S variant enhanced cell migration and PDGF-stimulated Erk1/2 activation, suggesting a dominant negative interference with endogenous DEP-1. In contrast to cell migration, cell–substrate adhesion was promoted by active DEP-1 and delayed or suppressed by DEP-1 C1239S, correlating with positive effects of DEP-1 on adhesion-stimulated Src kinase. We propose that negative regulation of growth-factor stimulated cell migration and promotion of cell–matrix adhesion may be related to the function of DEP-1 as tumor suppressor.

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References

  • Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G and Page DL . (1991). Proc. Natl. Acad. Sci. USA, 88, 10435–10439.

  • Autschbach F, Palou E, Mechtersheimer G, Rohr C, Pirotto F, Gassler N, Otto HF, Schraven B and Gaya A . (1999). Tissue Antigens, 54, 485–498.

  • Baker JE, Majeti R, Tangye SG and Weiss A . (2001). Mol. Cell. Biol., 21, 2393–2403.

  • Blake RA, Broome MA, Liu X, Wu J, Gishizky M, Sun L and Courtneidge SA . (2000). Mol. Cell. Biol., 20, 9018–9027.

  • Borges LG, Seifert RA, Grant FJ, Hart CE, Disteche CM, Edelhoff S, Solca FF, Lieberman MA, Lindner V, Fischer EH, Lok S and Bowen-Pope DF . (1996). Circ. Res., 79, 570–580.

  • Cheng A, Bal GS, Kennedy BP and Tremblay ML . (2001). J. Biol. Chem., 276, 25848–25855.

  • Chiarugi P, Cirri P, Taddei L, Giannoni E, Camici G, Manao G, Raugei G and Ramponi G . (2000). J. Biol. Chem., 275, 4640–4646.

  • Chiarugi P, Cirri P, Taddei ML, Talini D, Doria L, Fiaschi T, Buricchi F, Giannoni E, Camici G, Raugei G and Ramponi G . (2002). J. Cell Sci., 115, 2219–2232.

  • Claesson-Welsh L . (1996). Int. J. Biochem. Cell Biol., 28, 373–385.

  • Cooper JA, Esch FS, Taylor SS and Hunter T . (1984). J. Biol. Chem., 259, 7835–7841.

  • Courtneidge SA, Fumagalli S, Koegl M, Superti-Furga G and Twamley-Stein GM . (1993). Dev. Suppl., 57–64.

  • de la Fuente-Garcia MA, Nicolas JM, Freed JH, Palou E, Thomas AP, Vilella R, Vives J and Gaya A . (1998). Blood, 91, 2800–2809.

  • de Rooij J and Bos JL . (1997). Oncogene, 14, 623–625.

  • Frame MC, Fincham VJ, Carragher NO and Wyke JA . (2002). Nat. Rev. Mol. Cell Biol., 3, 233–245.

  • Graness A, Adomeit A, Ludwig B, Müller WD, Kaufmann R and Liebmann C . (1997). Biochem. J., 327, 147–154.

  • Gross S, Knebel A, Tenev T, Neininger A, Gaestel M, Herrlich P and Böhmer FD . (1999). J. Biol. Chem., 274, 26378–26386.

  • Hansen K, Johnell M, Siegbahn A, Rorsman C, Engström U, Wernstedt C, Heldin CH and Rönnstrand L . (1996). EMBO J., 15, 5299–5313.

  • Harder KW, Moller NP, Peacock JW and Jirik FR . (1998). J. Biol. Chem., 273, 31890–31900.

  • Heldin CH, Östman A and Rönnstrand L . (1998). Biochim. Biophys. Acta, 1378, F79–F113.

  • Heldin CH and Westermark B . (1999). Physiol. Rev., 79, 1283–1316.

  • Holsinger LJ, Ward K, Duffield B, Zachwieja J and Jallal B . (2002). Oncogene, 21, 7067–7076.

  • Hundt M and Schmidt RE . (1997). Eur. J. Immunol., 27, 3532–3535.

  • Iuliano R, Trapasso F, Le Pera I, Schepis F, Sama I, Clodomiro A, Dumon KR, Santoro M, Chiariotti L, Viglietto G and Fusco A . (2003). Cancer Res., 63, 882–886.

  • Iuliano R, Trapasso F, Sama I, Le Pera I, Martelli ML, Lembo F, Santoro M, Viglietto G, Chiariotti L and Fusco A . (2001). FEBS Lett., 500, 41–44.

  • Jallal B, Mossie K, Vasiloudis G, Knyazev P, Zachwieja J, Clairvoyant F, Schilling J and Ullrich A . (1997). J. Biol. Chem., 272, 12158–12163.

  • Keane MM, Lowrey GA, Ettenberg SA, Dayton MA and Lipkowitz S . (1996). Cancer Res., 56, 4236–4243.

  • Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P and Cheresh DA . (1997). J. Cell Biol., 137, 481–992.

  • Klinghoffer RA, Sachsenmaier C, Cooper JA and Soriano P . (1999). EMBO J., 18, 2459–2471.

  • Kovalenko M, Denner K, Sandström J, Persson C, Gross S, Jandt E, Vilella R, Böhmer FD and Östman A . (2000). J. Biol. Chem., 275, 16219–16226.

  • Kovalenko M, Gazit A, Böhmer A, Rorsman C, Rönnstrand L, Heldin CH, Waltenberger J, Böhmer FD and Levitzki A . (1994). Cancer Res., 54, 6106–6114.

  • Mahboobi S, Teller S, Pongratz H, Hufsky H, Sellmer A, Botzki A, Uecker A, Beckers T, Baasner S, Schachtele C, Überall F, Kassack MU, Dove S and Böhmer FD . (2002). J. Med. Chem., 45, 1002–1018.

  • Östman A and Böhmer FD . (2001). Trends Cell Biol., 11, 258–266.

  • Östman A, Yang Q and Tonks NK . (1994). Proc. Natl. Acad. Sci. USA, 91, 9680–9684.

  • Palka HL, Park M and Tonks NK . (2003). J. Biol. Chem., 278, 5728–5735.

  • Persson C, Engström U, Mowbray SL and Östman A . (2002). FEBS Lett., 517, 27–31.

  • Roche S, Koegl M, Barone MV, Roussel MF and Courtneidge SA . (1995). Mol. Cell. Biol., 15, 1102–1109.

  • Rönnstrand L, Arvidsson AK, Kallin A, Rorsman C, Hellman U, Engström U, Wernstedt C and Heldin CH . (1999a). Oncogene, 18, 3696–3702.

  • Rönnstrand L and Heldin CH . (2001). Int. J .Cancer., 91, 757–762.

  • Rönnstrand L, Siegbahn A, Rorsman C, Johnell M, Hansen K and Heldin CH . (1999b). J. Biol. Chem., 274, 22089–22094.

  • Rönnstrand L, Terracio L, Claesson-Welsh L, Heldin CH and Rubin K . (1988). J. Biol. Chem., 263, 10429–10435.

  • Ruivenkamp CA, Van Wezel T, Zanon C, Stassen AP, Vlcek C, Csikos T, Klous AM, Tripodis N, Perrakis A, Boerrigter L, Groot PC, Lindeman J, Mooi WJ, Meijjer GA, Scholten G, Dauwerse H, Paces V, Van Zandwijk N, Van Ommen GJ and Demant P . (2002). Nat. Genet., 31, 295–300.

  • Salazar EP and Rozengurt E . (2001). J. Biol. Chem., 276, 17788–17795.

  • Schraven B . (2000). J. Biol. Regul. Homeost. Agents., 14, 220–222.

  • Sörby M, Sandström J and Östman A . (2001). Oncogene, 20, 5219–5224.

  • Takahashi T, Takahashi K, Mernaugh R, Drozdoff V, Sipe C, Schoecklmann H, Robert B, Abrahamson DR and Daniel TO . (1999). J. Am. Soc. Nephrol., 10, 2135–2145.

  • Takahashi T, Takahashi K, St John PL, Fleming PA, Tomemori T, Watanabe T, Abrahamson DR, Drake CJ, Shirasawa T and Daniel TO . (2003). Mol. Cell. Biol., 23, 1817–1831.

  • Tangye SG, Phillips JH, Lanier LL, de Vries JE and Aversa G . (1998a). J. Immunol., 161, 3249–3255.

  • Tangye SG, Wu J, Aversa G, de Vries JE, Lanier LL and Phillips JH . (1998b). J. Immunol., 161, 3803–3807.

  • Tenev T, Böhmer SA, Kaufmann R, Frese S, Bittorf T, Beckers T and Böhmer FD . (2000). Eur. J. Cell. Biol., 79, 261–271.

  • Venable CL, Frevert EU, Kim YB, Fischer BM, Kamatkar S, Neel BG and Kahn BB . (2000). J. Biol. Chem., 275, 18318–18326.

  • Zhang L, Martelli ML, Battaglia C, Trapasso F, Tramontano D, Viglietto G, Porcellini A, Santoro M and Fusco A . (1997). Exp. Cell. Res., 235, 62–70.

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Acknowledgements

This work was supported by Grant BO1043-4 from the Deutsche Forschungsgemeinschaft, Grant 01EA0103 from BMBF and by a travel grant from DAAD. We gratefully acknowledge provision of an antibody by Dr J Vives. We are indebted to Mrs Andrea Uecker for expert technical assistance.

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Author notes

  1. Karsten Denner

    Present address: Research Laboratories, Schering AG, D-13342, Berlin, Germany

  2. Marina Kovalenko

    Present address: Schepens Eye Research Institute, 20 Staniford St, Boston, MA, 02114, USA

Authors and Affiliations

  1. Research Unit Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Drackendorfer str 1 D-07747 Jena, Germany

    Enrico Jandt, Karsten Denner & Frank-D Böhmer

  2. Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, S-75123, Sweden

    Marina Kovalenko & Arne Östman

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  1. Enrico Jandt
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Correspondence to Frank-D Böhmer.

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Jandt, E., Denner, K., Kovalenko, M. et al. The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion. Oncogene 22, 4175–4185 (2003). https://doi.org/10.1038/sj.onc.1206652

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