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The distinct capacity of Fyn and Lck to phosphorylate Sam68 in T cells is essentially governed by SH3/SH2-catalytic domain linker interactions

Oncogene volume 21, pages 7205–7213 (2002)Cite this article

Abstract

Sam68 phosphorylation correlates with Fyn but not Lck expression in T cells. This substrate has been used here to explore the possible basis of the specificity of Fyn versus Lck. We show that this specificity is not based on a spatial segregation of the two kinases, since a chimeric Lck molecule containing the membrane anchoring domain of Fyn does not phosphorylate Sam68. Moreover, a Sam68 molecule targeted to the plasma membrane by the farnesylation signal of c-Ha-Ras remains poorly phosphorylated by Lck. In T cells, Fyn appears to be the active Src kinase in rafts, but Sam68 is not expressed in rafts, and its distinct phosphorylation by Fyn and Lck is not affected by raft dispersion. The Fyn/Lck specificity does not reflect a higher kinase activity of Fyn in general, as both Fyn and Lck are similarly recognized by an anti-active Src antibody. Both also strongly phosphorylate another Src substrate in vivo. Mainly, Lck phosphorylates Sam68 when the interaction between the SH3 domain and the SH2-catalytic domain linker is altered in heterologous Src molecules or after mutating key residues in the linker that increase the accessibility of the SH3 domain. Thus, the distinct potential of Fyn and Lck to phosphorylate Sam68 is likely controlled by the interaction of the kinase SH3 domain with the linker and Sam68, possibly on a competitive binding basis.

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References

  • Abrams CS, Zhao W . 1995 J. Biol. Chem. 270: 333–339

  • Alexandropoulos K, Baltimore D . 1996 Genes Dev. 10: 1341–1355

  • Appleby MW, Gross JA, Cooke MP, Levin SD, Qian X, Perlmutter RM . 1992 Cell 70: 751–763

  • Barlat I, Maurier F, Duchesne M, Guitard E, Tocque B, Schweighoffer F . 1997 J. Biol. Chem. 272: 3129–3132

  • Cartwright CA, Eckhart W, Simon S, Kaplan PL . 1987 Cell 49: 83–91

  • Chen T, Damaj BB, Herrera C, Lasko P, Richard S . 1997 Mol. Cell. Biol. 17: 5707–5718

  • Cooper JA, Gould KL, Cartwright CA, Hunter T . 1986 Science 231: 1431–1434

  • da Silva AJ, Li Z, de Vera C, Canto E, Findell P, Rudd CE . 1997 Proc. Natl. Acad. Sci. USA 94: 7493–7498

  • Davidson D, Chow LM, Veillette A . 1997 J. Biol. Chem. 272: 1355–1362

  • Feshchenko EA, Langdon WY, Tsygankov AY . 1998 J. Biol. Chem. 273: 8323–8331

  • Fumagalli S, Totty NF, Hsuan JJ, Courtneidge SA . 1994 Nature 368: 871–874

  • Fusaki N, Iwamatsu A, Iwashima M, Fujisawa J . 1997 J. Biol. Chem. 272: 6214–6219

  • Gonfloni S, Frischknecht F, Way M, Superti-Furga G . 1999 Nat. Struct. Biol. 6: 760–764

  • Gonfloni S, Weijland A, Kretzschmar J, Superti-Furga G . 2000 Nat. Struct. Biol. 7: 281–286

  • Gonfloni S, Williams JC, Hattula K, Weijland A, Wierenga RK, Superti-Furga G . 1997 EMBO J. 16: 7261–7271

  • Groves T, Smiley P, Cooke MP, Forbush K, Perlmutter RM, Guidos CJ . 1996 Immunity 5: 417–428

  • Hartley DA, Hurley TR, Hardwick JS, Lund TC, Medveczky PG, Sefton BM . 1999 J. Biol. Chem. 274: 20056–20059

  • Hiroaki H, Klaus W, Senn H . 1996 J. Biomol. NMR. 8: 105–122

  • Itoh K, Sakakibara M, Yamasaki S, Takeuchi A, Arase H, Miyazaki M, Nakajima N, Okada M, Saito T . 2002 J. Immunol. 168: 541–544

  • Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C . 1998 J. Immunol. 161: 2798–2803

  • Kabouridis PS, Janzen J, Magee AL, Ley SC . 2000 Eur. J. Immunol. 30: 954–963

  • Kawabuchi M, Satomi Y, Takao T, Shimonishi Y, Nada S, Nagai K, Tarakhovsky A, Okada M . 2000 Nature 404: 999–1003

  • Klages S, Adam D, Class K, Fargnoli J, Bolen JB, Penhallow RC . 1994 Proc. Natl. Acad. Sci. USA 91: 2597–2601

  • Kmiecik TE, Shalloway D . 1987 Cell 49: 65–73

  • Lang V, Mege D, Semichon M, Gary-Gouy H, Bismuth G . 1997 Eur. J. Immunol. 27: 3360–3367

  • Lang V, Semichon M, Michel F, Brossard C, Gary-Gouy H, Bismuth G . 1999 J. Immunol. 162: 7224–7232

  • Ley SC, Marsh M, Bebbington CR, Proudfoot K, Jordan P . 1994 J. Cell. Biol. 125: 639–649

  • Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B . 1997 J. Biol. Chem. 272: 16077–16080

  • Marie-Cardine A, Kirchgessner H, Schraven B . 1999 Eur. J. Immunol. 29: 1175–1187

  • Marie-Cardine A, Verhagen AM, Eckerskorn C, Schraven B . 1998 FEBS Lett. 435: 55–60

  • Moarefi I, LaFevre-Bernt M, Sicheri F, Huse M, Lee CH, Kuriyan J, Miller WT . 1997 Nature 385: 650–653

  • Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann KU, Veillette A . 1992 Nature 357: 161–164

  • Mustelin T, Altman A . 1990 Oncogene 5: 809–813

  • Mustelin T, Coggeshall KM, Altman A . 1989 Proc. Natl. Acad. Sci. USA 86: 6302–6306

  • Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H . 1991 Nature 351: 69–72

  • Nemorin JG, Duplay P . 2000 J. Biol. Chem. 275: 14590–14597

  • Okada M, Nada S, Yamanashi Y, Yamamoto T, Nakagawa H . 1991 J. Biol. Chem. 266: 24249–24252

  • Ostermeyer AG, Beckrich BT, Ivarson KA, Grove KE, Brown DA . 1999 J. Biol. Chem. 274: 34459–34466

  • Piwnica-Worms H, Saunders KB, Roberts TM, Smith AE, Cheng SH . 1987 Cell 49: 75–82

  • Prior IA, Harding A, Yan J, Sluimer J, Parton RG, Hancock JF . 2001 Nat. Cell. Biol. 3: 368–375

  • Qian D, Lev S, van Oers NS, Dikic I, Schlessinger J, Weiss A . 1997 J. Exp. Med. 185: 1253–1259

  • Richard S, Yu D, Blumer KJ, Hausladen D, Olszowy MW, Connelly PA, Shaw AS . 1995 Mol. Cell. Biol. 15: 186–197

  • Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF . 1999 Oncogene 18: 4647–4653

  • Sicheri F, Moarefi I, Kuriyan J . 1997 Nature 385: 602–609

  • Stein PL, Lee HM, Rich S, Soriano P . 1992 Cell 70: 741–750

  • Takemoto Y, Furuta M, Li XK, Strong-Sparks WJ, Hashimoto Y . 1995 EMBO J. 14: 3403–3414

  • Takemoto Y, Sato M, Furuta M, Hashimoto Y . 1996 Int. Immunol. 8: 1699–1705

  • Taylor SJ, Shalloway D . 1994 Nature 368: 867–871

  • Torgersen KM, Vang T, Abrahamsen H, Yaqub S, Horejsi V, Schraven B, Rolstad B, Mustelin T, Tasken K . 2001 J. Biol. Chem. 276: 29313–29318

  • Tsygankov AY, Mahajan S, Fincke JE, Bolen JB . 1996 J. Biol. Chem. 271: 27130–27137

  • van Oers NS, Lowin-Kropf B, Finlay D, Connolly K, Weiss A . 1996 Immunity 5: 429–436

  • Vernet C, Artzt K . 1997 Trends Genet. 13: 479–484

  • Williams JC, Weijland A, Gonfloni S, Thompson A, Courtneidge SA, Superti-Furga G, Wierenga RK . 1997 J. Mol. Biol. 274: 757–775

  • Williams JC, Wierenga RK, Saraste M . 1998 Trends Biochem. Sci. 23: 179–184

  • Xu W, Doshi A, Lei M, Eck MJ, Harrison SC . 1999 Mol. Cell. 3: 629–638

  • Xu W, Harrison SC, Eck MJ . 1997 Nature 385: 595–602

  • Yamaguchi H, Hendrickson WA . 1996 Nature 384: 484–489

  • Yang WC, Ghiotto M, Barbarat B, Olive D . 1999 J. Biol. Chem. 274: 607–617

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Acknowledgements

We thank Drs A Trautmann, C Randriamampita and V Lang for their critical reading of the manuscript and helpful suggestions. We are grateful to Dr G Superti-Furga for the Src(SH3)Lck construct. This work was supported in part by grants from the Association de la Recherche contre le Cancer and by grants from the Ligue Nationale contre le Cancer. V Feuillet is a recipient of a graduate studentship from the Ministère de l'Education Nationale et de la Recherche. M Semichon is supported by Association Claude Bernard. A Restouin is a recipient of a SIDACTION fellowship. J Harriague is a recipient of a Fondation pour la Recherche Médicale fellowship. J Janzen is supported by Leukemia Research Fund grant 9705.

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Authors and Affiliations

  1. Département de Biologie Cellulaire, INSERM U.567, CNRS UMR 8104, Université René Descartes, Institut Cochin. Laboratoire labellisé par la Ligue Nationale contre le Cancer, Paris, 75014, France

    Vincent Feuillet, Monique Semichon, Julie Harriague & Georges Bismuth

  2. INSERM U119, Institut Paoli Calmette, Marseille, 13009, France

    Audrey Restouin & Yves Collette

  3. Division of Biomedical Sciences, Section of Cell and Molecular Biology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, UK

    Julia Janzen & Anthony Magee

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  1. Vincent Feuillet
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Correspondence to Georges Bismuth.

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Feuillet, V., Semichon, M., Restouin, A. et al. The distinct capacity of Fyn and Lck to phosphorylate Sam68 in T cells is essentially governed by SH3/SH2-catalytic domain linker interactions. Oncogene 21, 7205–7213 (2002). https://doi.org/10.1038/sj.onc.1205929

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