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Differential interaction and activation of Rho family GTPases by p210bcr-abl and p190bcr-abl

Oncogene volume 22, pages 6445–6454 (2003)Cite this article

Abstract

The p210bcr-abl and p190bcr-abl fusion proteins, respectively responsible for chronic myelogenous leukemia and acute lymphoblastic leukemia, present deregulated tyrosine kinase activity and abnormal localization. The Dbl homology domain of Bcr, activating Rho GTPases, is present in p210bcr-abl, but absent in p190bcr-abl. We investigated the interaction of Bcr-Abl chimeras and Rho proteins by coimmunoprecipitation, pull-down experiments and GEF activity measurement. RhoA, Rac1 and Cdc42 interact in vivo with p210bcr-abl only. Moreover, the three types of GTPases are activated in vitro and in vivo by p210bcr-abl. Nevertheless, Rac1 and Cdc42, but not RhoA, are activated by p190bcr-abl in vitro and in vivo. Part of this GEF activity of p190bcr-abl is probably attributable to p95vav, which is complexed with both p190bcr-abl and p210bcr-abl in an activated form. p160bcr, also in complex with Bcr-Abl, presents no GEF activity in p190bcr-abl-expressing cells. These results suggest that differential activation of Rho proteins should play a major role in Bcr-Abl-induced leukemogenesis.

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References

  • Adamson P, Paterson HF and Hall A . (1992). J. Cell Biol., 119, 617–627.

  • Aghazadeh B, Lowry WE, Huang X-Y and Rosen MK . (2000). Cell., 102, 625–633.

  • Bassermann F, Jahn T, Miething C, Seipel P, Bai RY, Coutinho S, Tybulewicz VL, Peschel C and Duyster J . (2002). J. Biol. Chem., 277, 12437–12445.

  • Bazzoni G, Carlesso N, Griffin JD and Hemler ME . (1996). J. Clin. Invest., 98, 521–528.

  • Burstein ES, Hesterberg DJ, Gutkind JS, Brann MR, Currier EA and Messier TL . (1998). Oncogene, 17, 1617–1623.

  • Campbell ML, Li W and Arlinghaus RB . (1990). Oncogene, 5, 773–776.

  • Cheng JC, Frackelton Jr AR, Bearer EL, Kumar PS, Kannan B, Santos-Moore A, Rifai A, Settleman J and Clark JW . (1995). Cell Growth Differ., 6, 139–148.

  • Chuang T-H, Xu X, Kaartinen V, Heisterkamp N, Groffen J and Bokoch G . (1995). Proc. Natl. Acad. Sci. USA, 92, 10282–10286.

  • Clark SS, McLaughlin J, Timmons M, Pendergast AM, Ben-Neriah Y, Dow LW, Crist G, Rovera W, Smith SD and Witte ON . (1988). Science, 239, 775–777.

  • Crespo P, Bustelo XR, Aaronson DS, Coso OA, Lopez-Barahona M, Barbacid M and Gutkind JS . (1996). Oncogene, 13, 455–460.

  • Daley GQ and Baltimore D . (1988). Proc. Natl. Acad. Sci. USA, 85, 9312–9316.

  • Daley GQ, Van Etten RA and Baltimore D . (1990). Science, 247, 824–830.

  • Das B, Shu X, Day GJ, Han J, Krishna UM, Falck JR and Broeck D . (2000). J. Biol. Chem., 275, 15074–15081.

  • Druker B, Okuda K, Matulonis U, Salgia R, Roberts T and Griffin JD . (1992). Blood, 79, 2215–2220.

  • Eda M, Yonemura S, Kato T, Watanabe N, Ishizaki T, Madaule P and Narumiya S . (2001). J. Cell Sci., 114, 3273–3284.

  • Han J, Das B, Wie W, Van Aelst L, Mosteller RD, Kosravi-Far R, Westwick JK, Der CJ and Broeck D . (1997). Mol. Cell. Biol., 17, 1346–1353.

  • Hansen MD and Nelson WJ . (2001). Curr. Biol., 11, 356–360.

  • Hart M, Eva A, Evans T, Aaronson SA and Cerione RA . (1991). Nature, 354, 311–315.

  • Hoshino M, Sone M, Fukata M, Kuroda S, Kaibuchi K, Nabeshima Y and Hama C . (1999). J. Biol. Chem., 274, 17837–17844.

  • Ilaria Jr RL and Van Etten RA . (1996). J. Biol. Chem., 271, 31704–31710.

  • Laëmmli UK and Favre M . (1973). J. Mol. Biol., 80, 575–599.

  • Li S, Ilaria Jr RL, Million RP, Daley GQ and Van Etten RA . (1999). J. Exp. Med., 189, 1399–1412.

  • Lipp é R, Miaczynska M, Rybin V, Runge A and Zerial M . (2001). Mol. Biol. Cell., 12, 2219–2228.

  • Lugo TG, Pendergast A-M, Muller AJ and Witte ON . (1990). Science, 247, 1079–1082.

  • Matsuguchi T, Inborn RC, Carlesso N, Xu G, Druker B and Griffin JD . (1995). EMBO J., 14, 257–265.

  • McWhirter JR, Gallasso DL and Wang JYJ . (1993). Mol. Cell. Biol., 13, 7587–7595.

  • McWhirter JR and Wang JYJ . (1993). EMBO J., 12, 1533–1546.

  • Missy K, Van Poucke V, Raynal P, Viala C, Mauco G, Plantavid M, Chap H and Payrastre B . (1998). J. Biol. Chem., 273, 30279–30286.

  • Nakashima S and Nozawa Y . (1999). Chem. Phys. Lipids, 98, 153–164.

  • Nishida K, Kaziro Y and Satoh T . (1999). Oncogene, 18, 407–415.

  • Nobes CD and Hall A . (1999). J. Cell Biol., 144, 1235–1244.

  • Ohguchi K, Nakashima S, Tan Z, Banno Y, Dohi S and Nozawa Y . (1997). J. Biol. Chem., 272, 1990–1996.

  • Olson MF, Pasteris NG, Gorski JL and Hall A . (1996). Curr. Biol., 6, 1628–1633.

  • Olson MF, Paterson HF and Marshall CJ . (1998). Nature, 394, 295–298.

  • Pear W, Nolan GP, Scott ML and Baltimore D . (1993). Proc. Natl. Acad. Sci. USA, 90, 8392–8396.

  • Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, Arlinghaus R and Pawson T . (1994). EMBO J., 13, 764–773.

  • Qiu R-G, Chen J, Kirn D, McCormick F and Symons M . (1995). Nature, 374, 457–459.

  • Quackenbush RC, Reuther GW, Miller JP, Courtney KD, Pear WS and Pendergast AM . (2000). Blood, 95, 2913–2921.

  • Roig J, Tuazon PT, Zipfel PA, Pendergast AM and Traugh JA . (2000). Proc. Natl. Acad. Sci. USA, 97, 14346–14351.

  • Rudolph MG, Linnemann T, Grunewald P, Wittinghofer A, Vetter IR and Herrmann C . (2001). J. Biol. Chem., 276, 23914–23921.

  • Salgia R, Brunkhorst B, Pisick E, Li J-L, Lo SH, Chen LB and Griffin JD . (1995). Oncogene., 11, 1149–1155.

  • Salgia R, Li J-L, Ewaniuk DS, Pear W, Pisick E, Burky SA, Ernst T, Sattler M, Chen LB and Griffin JD . (1997). J. Clin. Invest., 100, 46–57.

  • Sander EE, ten Klooster JP, van Delft S, van der Kammen RA and Collard JG . (1999). J. Cell Biol., 147, 1009–1021.

  • Sander EE, van Delft S, ten Klooster JP, Reid T, van der Kammen RA, Michiels F and Collard JG . (1998). J. Cell Biol., 143, 1385–1398.

  • Skorski T, Bellacosa A, Nieborowska-Skorska M, Majewski M, Martinez R, Choi JK, Trotta R, Wlodarski P, Perotti D, Chan TO, Wazik MA, Tsichlis PN and Calabretta B . (1997). EMBO J., 16, 6151–6161.

  • Skorski T, Kanakaraj P, Nieborowska-skorska M, Ratajczak MZ, Wen SC, Zon G, Gewirtz AM, Perussia B and Calabretta B . (1995). Blood, 86, 726–736.

  • Skorski T, Wlodarski P, Daheron L, Salomon P, Nieborowska-Skorska M, Majewski M, Wazik M and Calabretta B . (1998). Proc. Natl. Acad. Sci. USA, 95, 11858–11862.

  • Skourides PA, Perera SA and Ren R . (1999). Oncogene, 18, 1165–1176.

  • Tapon N and Hall A . (1997). Curr. Opin. Cell Biol., 9, 86–92.

  • Tolias KF, Cantley LC and Carpenter CL . (1995). J. Biol. Chem., 270, 17656–17659.

  • Van Etten RA . (1999). Trends Cell Biol., 9, 179–186.

  • Verfaillie CM, Hurley R, Lundell BI, Zao C and Bahtia R . (1995). Acta Haematol., 97, 40–52.

  • Voncken JW, van Shaick H, Kaartinen V, Deemer K, Coates T, Landing B, Pattengale P, Dorseuil O, Bokoch GM, Groffen J and Heisterkamp N . (1995). Cell, 80, 719–728.

  • Wu Y, Ma G, Lu D, Lin F, Xu HJ, Liu J and Arlinghaus RB . (1999). Oncogene, 18, 4416–4424.

  • Zhu X, Boman AL, Kuai J, Ciepak W and Kahn RA . (2000). J. Biol. Chem., 275, 13465–13475.

  • Zohn IM, Campbell SL, Khosravi-Far R, Rossman KL and Der CJ . (1998). Oncogene, 17, 1415–1438.

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Acknowledgements

We thank George Daley and Rick Van Etten for providing us material and encouragement for this work. We also thank Bernard Payrastre and Alan Hall for GST-fused GTPases, and J Collard for sending us GST-PAK-CRIB and GST-RTK with the complete protocol. We also thank Rick Van Etten and Jean de Gunsburg for interesting helpful discussions, and Valérie Tourenne for helpful technical assistance. This work was in part supported by grants provided by the ‘Ligue Nationale centre le Cancer, Charente-maritime and Vienne’.

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  1. Laboratoire de Génétique Cellulaire et Moléculaire, UPRES EA2622, CHU de Poitiers, BP 577, Poitiers Cedex, 86021, France

    Thomas Harnois, Agnès Rioux, Eddy Grenioux, Alain Kitzis & Nicolas Bourmeyster

  2. Laboratoire de Biomembranes et Signalisation Cellulaire, UMR CNRS 6558, 40, Av. du Recteur Pineau, Poitiers Cedex, 86022, France

    Bruno Constantin

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Correspondence to Alain Kitzis.

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Harnois, T., Constantin, B., Rioux, A. et al. Differential interaction and activation of Rho family GTPases by p210bcr-abl and p190bcr-abl. Oncogene 22, 6445–6454 (2003). https://doi.org/10.1038/sj.onc.1206626

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