Résumés
Résumé
La tyrosine kinase ZAP-70 (zeta-chain-associated protein of 70 kDa) a connu son heure de gloire au début des années 1990, lorsque des mutations du gène codant pour cette protéine ont été mises en évidence chez de très jeunes patients présentant des déficits immunitaires combinés sévères. La caractérisation, chez ces patients, de déficits fonctionnels des lymphocytes T signait le rôle crucial de cette protéine dans l’activation de ces cellules. Très récemment, un regain d’intérêt pour ZAP-70 est apparu lorsque son expression, dans un premier temps considérée comme spécifique des lymphocytes T et des cellules NK (natural killer), a été mise en évidence dans certaines leucémies lymphoïdes chroniques B et associée à un facteur pronostique. Enfin, la découverte d’une mutation ponctuelle spontanée de ZAP-70 dans une souche de souris présentant une arthrite rhumatoïde révélait également le rôle potentiel de ZAP-70 dans des maladies auto-immunes. Les diverses maladies associées à des modifications d’expression ou d’activité de ZAP-70 démontrent le rôle clé de cette kinase dans la mise en place et la régulation d’une réponse immunitaire.
Summary
The ZAP-70 tyrosine kinase has been described more than ten years ago. Its key role in thymocytes development and mature T lymphocytes activation has been illustrated by the characterization of several human immunodeficiencies presenting with mutations in the zap-70 gene resulting in the absence of ZAP-70 expression. More recently, it has been shown that deregulation of ZAP-70 activity can induce autoimmune diseases. Finally, ZAP-70 expression has been shown in some B chronic lymphocytic leukaemia and correlated with bad prognosis of the disease. The diversity of pathologies associated with deregulation of ZAP-70 demonstrates its key role in immune responses. Research aiming at deciphering the different signalling pathways regulated by ZAP-70 will not only shed some lights on these pathologies, but will also help finding new pharmacological tools, targeting ZAP-70, designed to induce immunosuppression or tolerance.
Parties annexes
Références
- 1. Chan AC, Iwashima M, Turck CW, Weiss A. ZAP-70 : a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell 1992 ; 71 : 649-62.
- 2. Weiss A, Littman DR. Signal transduction by lymphocyte antigen receptors. Cell 1994 ; 76 : 263-74.
- 3. Arpaia E, Shahar M, Dadi H, et al. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell 1994 ; 76 : 947-58.
- 4. Elder ME, Lin D, Clever J, et al. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science 1994 ; 264 : 1596-9.
- 5. Chan AC, Kadlecek TA, Elder ME, et al. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science 1994 ; 264 : 1599-601.
- 6. Hivroz C, Fischer A. Immunodeficiency diseases. Multiple roles for ZAP-70. Curr Biol 1994 ; 4 : 731-3.
- 7. Steinberg M, Swainson L, Schwarz K, et al. Retrovirus-mediated transduction of primary ZAP-70-deficient human T cells results in the selective growth advantage of gene-corrected cells : implications for gene therapy. Gene Ther 2000 ; 7 : 1392-40.
- 8. Matsuda S, Suzuki-Fujimoto T, Minowa A, et al. Temperature-sensitive ZAP70 mutants degrading through a proteasome-independent pathway. Restoration of a kinase domain mutant by Cdc37. J Biol Chem 1999 ; 274 : 34515-8.
- 9. Katamura K, Tai G, Tachibana T, et al. Existence of activated and memory CD4+ T cells in peripheral blood and their skin infiltration in CD8 deficiency. Clin Exp Immunol 1999 ; 115 : 124-30.
- 10. Williams BL, Schreiber KL, Zhang W, et al. Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor : reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Mol Cell Biol 1998 ; 18 : 1388-99.
- 11. Kadlecek TA, van Oers NS, Lefrancois L, et al. Differential requirements for ZAP-70 in TCR signaling and T cell development. J Immunol 1998 ; 161 : 4688-94.
- 12. Meinl E, Lengenfelder D, Blank N, et al. Differential requirement of ZAP-70 for CD2-mediated activation pathways of mature human T cells. J Immunol 2000 ; 165 : 3578-83.
- 13. Shan X, Balakir R, Criado G, et al. Zap-70-independent Ca2+ mobilization and Erk activation in Jurkat T cells in response to T-cell antigen receptor ligation. Mol Cell Biol 2001 ; 21 : 7137-49.
- 14. Zhang W, Sloan-Lancaster J, Kitchen J, et al. LAT : the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 1998 ; 92 : 83-92.
- 15. Wardenburg JB, Fu C, Jackman JK, et al. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J Biol Chem 1996 ; 271 : 19641-4.
- 16. Jordan MS, Singer AL, Koretzky GA. Adaptors as central mediators of signal transduction in immune cells. Nat Immunol 2003 ; 4 : 110-6.
- 17. Goda S, Quale AC, Woods ML, et al. Control of TCR-mediated activation of beta 1 integrins by the ZAP-70 tyrosine kinase interdomain B region and the linker for activation of T cells adapter protein. J Immunol 2004 ; 172 : 5379-87.
- 18. Blanchard N, Di Bartolo V, Hivroz C. In the immune synapse, ZAP-70 controls T cell polarization and recruitment of signaling proteins but not formation of the synaptic pattern. Immunity 2002 ; 17 : 389-99.
- 19. van Der Merwe PA, Davis SJ. The immunological synapse : a multitasking system. Science 2002 ; 295 : 1479-80.
- 20. Dumont C, Blanchard N, Di Bartolo V, et al. TCR/CD3 down-modulation and zeta degradation are regulated by ZAP-70. J Immunol 2002 ; 169 : 1705-12.
- 21. Zhong L, Wu CH, Lee WH, Liu CP. Zeta-associated protein of 70 kDa (ZAP-70), but not Syk, tyrosine kinase can mediate apoptosis of T cells through the Fas/Fas ligand, caspase-8 and caspase-3 pathways. J Immunol 2004 ; 172 : 1472-82.
- 22. Carpino N, Turner S, Mekala D, et al. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity 2004 ; 20 : 37-46.
- 23. Sakaguchi N, Takahashi T, Hata H, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 2003 ; 426 : 454-60.
- 24. Rosenwald A, Alizadeh AA, Widhopf G, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001 ; 194 : 1639-47.
- 25. Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004 ; 363 : 105-11.
- 26. Chen L, Widhopf G, Huynh L, et al. Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood 2002 ; 100 : 4609-14.
- 27. Turner M, Mee PJ, Costello PS, et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 1995 ; 378 : 298-302.
- 28. Cheng AM, Rowley B, Pao W, et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 1995 ; 378 : 303-6.
- 29. Schweighoffer E, Vanes L, Mathiot A, et al. Unexpected requirement for ZAP-70 in pre-B cell development and allelic exclusion. Immunity 2003 ; 18 : 523-33.
- 30. Elder ME, Skoda-Smith S, Kadlecek TA, et al. Distinct T cell developmental consequences in humans and mice expressing identical mutations in the DLAARN motif of ZAP-70. J Immunol 2001 ; 166 : 656-61.