Immunodeficiencies caused by genetic defects in protein kinases

Current Opinion in Immunology

Volumn 8, Issue 4, 1996, Pages 448-453

  Notarangelo, Luigi D ^a  

^a UNIVERSITY OF BRESCIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; CYTOKINE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; PROTEIN KINASE;

COMBINED IMMUNODEFICIENCY; GENE TARGETING; GENETIC DISORDER; HUMAN; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; NONHUMAN; PHENOTYPE; REVIEW; T LYMPHOCYTE ACTIVATION;

EID: 0030207577     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(96)80028-8     Document Type: Review

References (56)

1. Bolen JB. Protein tyrosine kinases in the initiation of antigen receptor signaling. Curr Opin Immunol. 7:1995;306-311.
2. Howe LR, Weiss A. Multiple kinases mediate T-cell-receptor signaling. Trends Biochem Sci. 20:1995;59-64.
3. DeFranco AL. Transmembrane signaling by antigen receptors of B and T lymphocytes. Curr Opin Cell Biol. 7:1995;163-175.
4. Taniguchi T. Cytokine signaling through nonreceptor protein tyrosine kinases. Science. 268:1995;251-255.
5. Ihle JN. Cytokine receptor signalling. Nature. 377:1995;591-594.
6. Weaver DT. What to do at an end: DNA double-strand-break repair. Trends Genet. 11:1995;388-392.
7. Molina TJ, Kishihara K, Siderovski DP, Ewijk W, Van Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann K-UU, Veillette A, et al. Profound block in thymocyte development in mice lacking p56lck. Nature. 357:1992;161-164.
8. lck in thymopoiesis. EMBO J. 12:1993;1671-1680.
9. Zinkernagel RM, Pircher HP, Ohashi PS, Oehen S, Odermatt B, Mak TW, Arnheiter H, Bürki K, Hengartner H. T and B cell tolerance and responses to viral antigens in transgenic mice: implications for the pathogenesis of autoimmune versus immunopathological disease. Immunol Rev. 122:1991;133-171.
10. Molina TJ, Bachmann MR, Kündig TM, Zinkernagel RM, Mak TW. Peripheral T cells in mice lacking p56lck do not express significant anti-viral effector mechanisms. J Immunol. 151:1993;699-706.
11. Fusaki N, Matsuda S, Nishizumi H, Umemori H, Yamamoto T. Physical and functional interactions of protein tyrosine kinases, p59fyn and ZAP-70, in T cell signaling. J Immunol. 156:1996;1369-1377.
12. Appleby MW, Gross JA, Cooke MP, Levin SD, Qian X, Perlmutter RM. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Cell. 70:1992;751-763.
13. Stein PL, Lee H-M, Rich S, Soriano P. p59fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell. 70:1992;741-750.
14. Hatada MH, Lu X, Laird ER, Green J, Morgenstern JP, Lou M, Marr CS, Phillips TB, Ram MK, Theriault K, et al. Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor. of special interest Nature. 377:1995;32-38 This paper describes the crystal structure of the tandem domains of human ZAP-70 in complex with a peptide derived from one of the ITAMs of the ζ chain of TCR, allowing for the characterization of the structural basis for the association between ZAP-70/Syk proteins and the TCR complex.
15. + thymic selection in humans lacking ZAP-70 kinase. Cell. 76:1994;947-958.
16. Elder ME, Lin D, Clever J, Chan AC, Hope TJ, Weiss A, Parslow TG. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science. 264:1994;1596-1599.
17. Chan AC, Kadlecek TA, Elder ME, Filipovich AH, Kuo W-L, Iwashima M, Parslow TG, Weiss A. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science. 264:1994;1599-1601.
18. Chan AC, Van Oers NSC, Tran A, Turka L, Law C-L, Ryan JC, Clark EA, Weiss A. Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 152:1994;4758-4766.
19. 70-/- mice, which are generated by gene targeting, is described. Lack of both CD4 and CD8 single-positive thymocytes, and defective negative selection, indicate the crucial role that ZAP-70 plays in T-cell development.
20. Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VLJ. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. of special interest Nature. 378:1995;298-302 See annotation [21].
21. -/- stem cells show selective and profound defects of B-cell differentiation, with intact T-cell development. These data illustrate the critical and non-redundant role of Syk in B-cell development.
22. Siliciano JD, Morrow TA, Desiderio SV. Itk a T-cell specific tyrosine kinase inducible by interleukin 2. Proc Natl Acad Sci USA. 89:1992;11194-11198.
23. August A, Gibson S, Kawakami Y, Kawakami T, Mills GB, Dupont B. CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. Proc Natl Acad Sci USA. 91:1994;9347-9351.
24. Liao XC, Littman DR. Altered T cell receptor signaling and disrupted T cell development in mice lacking ltk. of special interest Immunity. 3:1995;757-769 Mice deficient in Itk PTK were generated by gene targeting. The phenotype was characterized by decreased numbers of mature thymocytes and reduced proliferation of mature T cells in response to CD3 - TCR cross-linking.
25. Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen Y-Q, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR, O'Shea JJ. Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proc Natl Acad Sci USA. 91:1994;6374-6378.
26. Lai KS, Jin Y, Graham DK, Witthuhn BA, Ihle JN, Liu ET. A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells. J Biol Chem. 270:1995;25028-25036.
27. Miyazaki T, Kawahara A, Fuji H, Nakagawa Y, Minami Y, Liu Z-J, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN, Taniguchi T. Functional association of JAK1 and JAK3 by selective association with IL-2 receptor subunits. Science. 266:1994;1045-1047.
28. Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O, et al. Interaction of IL-2Rb and γc chains with JAK1 and JAK3: implications for X-SCID and X-CID. Science. 266:1994;1042-1045.
29. Kawahara AY, Minami T, Miyazaki T, Ihle JN, Taniguchi T. Critical role of the interleukin 2 (IL-2) receptor γ-chain-associated JAK3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction. of special interest Proc Natl Acad Sci USA. 92:1995;8724-8728 This study illustrate the critical role of JAK3 in IL-2-mediated responses. A dominant-negative form of JAK3, lacking the kinase domain, was transfected into an IL-2 responsive cell line. Overexpression of the JAK3 mutant resulted in strong inhibition of IL-2-induced phosphorylation of endogenous JAK1 and JAK3, of c-fos and c-myc induction, and of cellular proliferation.
30. Ihle JN. STATs: signal transducers and activators of transcription. Cell. 84:1996;331-334.
31. Hou J, Schindler U, Henzel WJ, Wong SC, McKnight SL. Identification and purification of human STAT proteins activated in response to interleukin-2. Immunity. 2:1995;321-329.
32. Johnston JA, Bacon CM, Finbloom DS, Rees RC, Kaplan D, Shibuya K, Ortaldo JR, Gupta S, Chen YQ, Giri JD, O'Shea JJ. Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukin 2 and 15. Proc Natl Acad Sci USA. 92:1995;8705-8709.
33. Lin J-X, Migone T-S, Tsang M, Friedmann M, Wheatherbee JA, Zhou L, Yamauchi A, Bloom ET, Mietz J, John S, Leonard WJ. The role of shared receptor motifs and common STAT proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity. 2:1995;331-339.
34. Gilmour JC, Pine R, Reich NC. Interleukin 2 activates STAT5 transcription factor (mammary gland factor) and specific gene expression in T lymphocytes. Proc Natl Acad Sci USA. 92:1995;10772-10776.
35. Johnston JA, Wang L-M, Hanson EP, Sun X-J, White MF, Oakes SA, Pierce JH, O'Shea JJ. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. J Biol Chem. 270:1995;28527-28530.
36. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ. Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 73:1993;147-157.
37. DiSanto JP, Müller W, Guy-Grand D, Fischer A, Rajewski K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor γ chain. of outstanding interest Proc Natl Acad Sci USA. 92:1995;377-381 See annotation [38].
38. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, et al. Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. of outstanding interest Immunity. 2:1995;223-228 These papers [37, 38] describe the phenotype of γc-gene targeted mice that present a profound defect on T-cell, B-cell and NK-cell differentiation. These findings illustrate the functional relevance of the γc chain in lymphoid development.
39. Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, et al. Mutations of JAK3 gene in patients with autosomal severe combined immune deficiency (SCID). of outstanding interest Nature. 377:1995;65-68 See annotation [40].
40. + SCID. The intrinsic nature of the B-cell defect is illustrated by failure of IL-4 to induce activation of STAT6 in the Epstein - Barr virus-transformed cell line from one of the patients.
41. Thomis DC, Gurniak CB, Tivol E, Sharpe AH, Berg LJ. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking JAK3. of outstanding interest Science. 270:1995;794-797 See annotation [43].
42. Nosaka T, Van Deursen JMA, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP, Doherty PC, Grosveld GC, Ihle JN. Defective lymphoid development in mice lacking JAK3. of outstanding interest Science. 270:1995;800-802 See annotation [43].
43. -/Y mice.
44. Boussiotis VA, Barber DL, Nakarai T, Freeman GJ, Gribben JG, Bernstein GM, D'Andrea AD, Ritz J, Nadler LM. Prevention of anergy by signaling through the γc chain of the IL-2 receptor. Science. 266:1994;1039-1042.
45. Bosma MJ, Carroll AM. The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol. 9:1991;323-350.
46. Hartley KO, Gell D, Smith GCM, Zhang H, Divecha N, Connelly MA, Admon A, Lees-Miller SP, Anderson CW, Jackson SP. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. of special interest Cell. 82:1995;849-856 This paper illustrates cloning of the human p450 DNA-PK gene, which shares homology with the ATM gene (mutated in ataxia-telangiectasia) and with the gene encoding PI3-K. Biochemical studies demonstrates that p450 DNA-PK is devoid of lipid kinase activity, whereas it has protein kinase activity.
47. Sipley JD, Menninger JC, Hartley KO, Ward DC, Jackson SP, Anderson CW. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci USA. 92:1995;7515-7519.
48. Boubnov NV, Weaver DT. SCID cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase. of special interest Mol Cell Biol. 15:1995;5700-5706 The authors demonstrate that murine SCID cells are deficient in the ability to phosphorylate Ku and replication protein A, two events dependent on DNA-PK. Introduction of human chromosome 8, expressing the DNA-PK catalytic subunit, reverts the phenotype.
49. Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. of special interest Science. 267:1995;1178-1182 This paper describes that p450 DNA-PK protein levels are diminished in cells from SCID mice; complementation studies showed that somatic-cell hybrids retaining human chromosome 8 (containing the p450 DNA-PK locus) were restored in V(D)J recombination and sensitivity to radiation.
50. Blunt T, Finnie NJ, Taccioli GE, Smith GCM, Demengeot J, Gottlieb TM, Mizuta R, Varghese AJ, Alt FW, Jeggo PA, Jackson SP. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. of special interest Cell. 80:1995;813-823 Defective activity of DNA-PK in SCID mice and in the V3 mutant hamster cell line results from deficiency in the DNA-PK catalytic subunit; addition of purified DNA-PK catalytic subunit to V3 or SCID cell extracts increased DNA-PK activity. Furthermore, yeast artificial chromosomes containing the DNA-PK catalytic subunit complemented DNA repair and recombination defects of V3 cells.
51. Miller RD, Hogg J, Ozaki JH, Gell D, Jackson SP, Riblet R. Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the SCID locus. Proc Natl Acad Sci USA. 92:1995;10792-10795.
52. Finnie NJ, Gottlieb TM, Blunt T, Jeggo PA, Jackson SP. DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-strand break repair. Proc Natl Acad Sci USA. 92:1995;320-324.
53. Boubnov NV, Hall KT, Wills Z, Lee SE, He DM, Benjamin DM, Pulaski CR, Band H, Reeves W, Hendrickson EA, Weaver DT. Complementation of the ionizing radiation sensitivity, DNA-end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen. Proc Natl Acad Sci USA. 92:1995;890-894.
54. Smider V, Rathmell WK, Lieber MR, Chu G. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science. 266:1994;288-291.
55. Schwarz K, Hansen-Hugge TE, Knobloch C, Friedrich W, Kleihauer E, Bartram C. Severe combined immunodeficiency (SCID) in man: B cell-negative (B-) SCID patients exhibit an irregular recombination pattern at the JH locus. J Exp Med. 174:1991;1039-1048.
56. Cavazzana-Calvo M, Le Deist F, De Saint Basile G, Papadopoulo D, De Villartay JP, Fischer A. Increased radiosensitivity of granulocyte macrophage colony-forming units and skin fibroblasts in human autosomal recessive severe combined immunodeficiency. J Clin Invest. 91:1993;1214-1218.