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Vol. 134, No. 1, 2004
Issue release date: May 2004
Int Arch Allergy Immunol 2004;134:65–78

The Role of Tec Family Kinases in Myeloid Cells

Schmidt U. · Boucheron N. · Unger B. · Ellmeier W.
aMedical University of Vienna, Institute of Immunology and bBMT-Vienna, Vienna, Austria

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Members of the Tec kinase family (Bmx, Btk, Itk, Rlk and Tec) are primarily expressed in the hematopoietic system and form, after the Src kinase family, the second largest class of non-receptor protein tyrosine kinases. During lymphocyte development and activation Tec kinases have important functions in signaling pathways downstream of the antigen receptors. Tec family kinases are also expressed in cells of the myeloid lineage. However, with the exception of mast cells and platelets, their biological role in the myeloid system is only poorly understood. This review summarizes the current knowledge about the function of Tec family kinases in hematopoietic cells of the myeloid lineage.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Mano H, Ishikawa F, Nishida J, Hirai H, Takaku F: A novel protein-tyrosine kinase, tec, is preferentially expressed in liver. Oncogene 1990;5:1781–1786.
  2. Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S, et al: Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993;72:279–290.
  3. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, Hammarstrom L, Kinnon C, Levinsky R, Bobrow M, et al: The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature 1993;361:226–233.
  4. Rawlings DJ, Saffran DC, Tsukada S, Largaespada DA, Grimaldi JC, Cohen L, Mohr RN, Bazan JF, Howard M, Copeland NG, et al: Mutation of unique region of Bruton’s tyrosine kinase in immunodeficient XID mice. Science 1993;261:358–361.
  5. Yamada N, Kawakami Y, Kimura H, Fukamachi H, Baier G, Altman A, Kato T, Inagaki Y, Kawakami T: Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells. Biochem Biophys Res Commun 1993;192:231–240.
  6. Tamagnone L, Lahtinen I, Mustonen T, Virtaneva K, Francis F, Muscatelli F, Alitalo R, Smith CI, Larsson C, Alitalo K: BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Oncogene 1994;9:3683–3688.
  7. Robinson D, He F, Pretlow T, Kung HJ: A tyrosine kinase profile of prostate carcinoma. Proc Natl Acad Sci USA 1996;93:5958–5962.
  8. Siliciano JD, Morrow TA, Desiderio SV: itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. Proc Natl Acad Sci USA 1992;89:11194–11198.
  9. Heyeck SD, Berg LJ: Developmental regulation of a murine T-cell-specific tyrosine kinase gene, Tsk. Proc Natl Acad Sci USA 1993;90:669–673.
  10. Haire RN, Ohta Y, Lewis JE, Fu SM, Kroisel P, Litman GW: TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. Hum Mol Genet 1994;3:897–901.
  11. Hu Q, Davidson D, Schwartzberg PL, Macchiarini F, Lenardo MJ, Bluestone JA, Matis LA: Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage. J Biol Chem 1995;270:1928–1934.
  12. Smith CI, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M: The Tec family of cytoplasmic tyrosine kinases: Mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays 2001;23:436–446.
  13. Schlessinger J: SH2/SH3 signaling proteins. Curr Opin Genet Dev 1994;4:25–30.
  14. Mayer BJ, Gupta R: Functions of SH2 and SH3 domains. Curr Top Microbiol Immunol 1998;228:1–22.
  15. Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL: Regulatory intramolecular association in a tyrosine kinase of the Tec family. Nature 1997;385:93–97.
  16. Cheng G, Ye ZS, Baltimore D: Binding of Bruton’s tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction. Proc Natl Acad Sci USA 1994;91:8152–8155.
  17. Debnath J, Chamorro M, Czar MJ, Schaeffer EM, Lenardo MJ, Varmus HE, Schwartzberg PL: rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases. Mol Cell Biol 1999;19:1498–1507.
  18. Mano H, Mano K, Tang B, Koehler M, Yi T, Gilbert DJ, Jenkins NA, Copeland NG, Ihle JN: Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit. Oncogene 1993;8:417–424.
  19. Kawakami Y, Yao L, Miura T, Tsukada S, Witte ON, Kawakami T: Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking. Mol Cell Biol 1994;14:5108–5113.
  20. Kawakami Y, Yao L, Tashiro M, Gibson S, Mills GB, Kawakami T: Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells. J Immunol 1995;155:3556–3562.
  21. Sommers CL, Huang K, Shores EW, Grinberg A, Charlick DA, Kozak CA, Love PE: Murine txk: A protein tyrosine kinase gene regulated by T cell activation. Oncogene 1995;11:245–251.
  22. Kazama A, Mano H, Morishita Y, Mori S: High expression of the tec gene product in murine testicular germ cells and erythroblasts. Pathol Int 1996;46:341–347.
  23. van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Lowenberg B, von Lindern M: Stem cell factor induces phosphatidylinositol 3′-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood 2000;96:3406–3413.
  24. Whyatt D, Lindeboom F, Karis A, Ferreira R, Milot E, Hendriks R, de Bruijn M, Langeveld A, Gribnau J, Grosveld F, Philipsen S: An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature 2000;406:519–524.
  25. Quek LS, Bolen J, Watson SP: A role for Bruton’s tyrosine kinase (Btk) in platelet activation by collagen. Curr Biol 1998;8:1137–1140.
  26. Laffargue M, Monnereau L, Tuech J, Ragab A, Ragab-Thomas J, Payrastre B, Raynal P, Chap H: Integrin-dependent tyrosine phosphorylation and cytoskeletal translocation of Tec in thrombin-activated platelets. Biochem Biophys Res Commun 1997;238:247–251.
  27. Kaukonen J, Lahtinen I, Laine S, Alitalo K, Palotie A: BMX tyrosine kinase gene is expressed in granulocytes and myeloid leukaemias. Br J Haematol 1996;94:455–460.
  28. Weil D, Power MA, Smith SI, Li CL: Predominant expression of murine Bmx tyrosine kinase in the granulo-monocytic lineage. Blood 1997;90:4332–4340.
  29. Horwood NJ, Mahon T, McDaid JP, Campbell J, Mano H, Brennan FM, Webster D, Foxwell BM: Bruton’s tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor alpha production. J Exp Med 2003;197:1603–1611.
  30. Lachance G, Levasseur S, Naccache PH: Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. Implication of phosphatidylinositol 3-kinases. J Biol Chem 2002;277:21537–21541.
  31. Gagliardi MC, Finocchi A, Orlandi P, Cursi L, Cancrini C, Moschese V, Miyawaki T, Rossi P: Bruton’s tyrosine kinase defect in dendritic cells from X-linked agammaglobulinaemia patients does not influence their differentiation, maturation and antigen-presenting cell function. Clin Exp Immunol 2003;133:115–122.
  32. Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA, Deanehan JK, Moore KA, Overton GC, Lemischka IR: The genetic program of hematopoietic stem cells. Science 2000;288:1635–1640.
  33. Yang EJ, Yoon JH, Chung KC: Bruton’s tyrosine kinase phosphorylates CREB at Ser-133 during neuronal differentiation in immortalized hippocampal progenitor cells. J Biol Chem 2004;279:1827–1837.
  34. Schaeffer EM, Schwartzberg PL: Tec family kinases in lymphocyte signaling and function. Curr Opin Immunol 2000;12:282–288.
  35. Lewis CM, Broussard C, Czar MJ, Schwartzberg PL: Tec kinases: Modulators of lymphocyte signaling and development. Curr Opin Immunol 2001;13:317–325.
  36. Miller AT, Berg LJ: New insights into the regulation and function of Tec family tyrosine kinases in the immune system. Curr Opin Immunol 2002;14:331–340.
  37. Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ: Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. J Biol Chem 2000;275:2219–2230.
  38. Guo B, Kato RM, Garcia-Lloret M, Wahl MI, Rawlings DJ: Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex. Immunity 2000;13:243–253.
  39. Shan X, Czar MJ, Bunnell SC, Liu P, Liu Y, Schwartzberg PL, Wange RL: Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation. Mol Cell Biol 2000;20:6945–6957.
  40. Woods ML, Kivens WJ, Adelsman MA, Qiu Y, August A, Shimizu Y: A novel function for the Tec family tyrosine kinase Itk in activation of beta 1 integrins by the T-cell receptor. EMBO J 2001;20:1232–1244.
  41. Takata M, Kurosaki T: A role for Bruton’s tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2. J Exp Med 1996;184:31–40.
  42. Fluckiger AC, Li Z, Kato RM, Wahl MI, Ochs HD, Longnecker R, Kinet JP, Witte ON, Scharenberg AM, Rawlings DJ: Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B-cell receptor activation. EMBO J 1998;17:1973–1985.
  43. Liu KQ, Bunnell SC, Gurniak CB, Berg LJ: T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. J Exp Med 1998;187:1721–1727.
  44. Schaeffer EM, Debnath J, Yap G, McVicar D, Liao XC, Littman DR, Sher A, Varmus HE, Lenardo MJ, Schwartzberg PL: Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science 1999;284:638–641.
  45. Donnadieu E, Lang V, Bismuth G, Ellmeier W, Acuto O, Michel F, Trautmann A: Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. J Immunol 2001;166:5540–5549.
  46. Hata D, Kawakami Y, Inagaki N, Lantz CS, Kitamura T, Khan WN, Maeda-Yamamoto M, Miura T, Han W, Hartman SE, Yao L, Nagai H, Goldfeld AE, Alt FW, Galli SJ, Witte ON, Kawakami T: Involvement of Bruton’s tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production. J Exp Med 1998;187:1235–1247.
  47. Su YW, Zhang Y, Schweikert J, Koretzky GA, Reth M, Wienands J: Interaction of SLP adaptors with the SH2 domain of Tec family kinases. Eur J Immunol 1999;29:3702–3711.
  48. Takesono A, Finkelstein LD, Schwartzberg PL: Beyond calcium: New signaling pathways for Tec family kinases. J Cell Sci 2002;115:3039–3048.
  49. Lucas JA, Miller AT, Atherly LO, Berg LJ: The role of Tec family kinases in T cell development and function. Immunol Rev 2003;191:119–138.
  50. Tsai YT, Su YH, Fang SS, Huang TN, Qiu Y, Jou YS, Shih HM, Kung HJ, Chen RH: Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. Mol Cell Biol 2000;20:2043–2054.
  51. Mahajan S, Vassilev A, Sun N, Ozer Z, Mao C, Uckun FM: Transcription factor STAT5A is a substrate of Bruton’s tyrosine kinase in B cells. J Biol Chem 2001;276:31216–31228.
  52. Yang W, Desiderio S: BAP-135, a target for Bruton’s tyrosine kinase in response to B cell receptor engagement. Proc Natl Acad Sci USA 1997;94:604–609.
  53. Webb CF, Yamashita Y, Ayers N, Evetts S, Paulin Y, Conley ME, Smith EA: The transcription factor Bright associates with Bruton’s tyrosine kinase, the defective protein in immunodeficiency disease. J Immunol 2000;165:6956–6965.
  54. Perez-Villar JJ, O’Day K, Hewgill DH, Nadler SG, Kanner SB: Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha). Int Immunol 2001;13:1265–1274.
  55. Takeba Y, Nagafuchi H, Takeno M, Kashiwakura J, Suzuki N: Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription. J Immunol 2002;168:2365–2370.
  56. Maas A, Hendriks RW: Role of Bruton’s tyrosine kinase in B cell development. Dev Immunol 2001;8:171–181.
  57. Rawlings DJ: Bruton’s tyrosine kinase controls a sustained calcium signal essential for B lineage development and function. Clin Immunol 1999;91:243–253.
  58. Mekori YA, Metcalfe DD: Mast cells in innate immunity. Immunol Rev 2000;173:131–140.

    External Resources

  59. Costello PS, Turner M, Walters AE, Cunningham CN, Bauer PH, Downward J, Tybulewicz VL: Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells. Oncogene 1996;13:2595–2605.
  60. Nishizumi H, Yamamoto T: Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation, in lyn-deficient bone marrow-derived mast cells. J Immunol 1997;158:2350–2355.
  61. Kawakami Y, Kitaura J, Satterthwaite AB, Kato RM, Asai K, Hartman SE, Maeda-Yamamoto M, Lowell CA, Rawlings DJ, Witte ON, Kawakami T: Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation. J Immunol 2000;165:1210–1219.
  62. Dvorak AM, Miura T, Letourneau L, Ishizaka T, Kawakami T: Spontaneous degranulation of cultured bone-marrow-derived immature mast cells from X-linked immunodeficient (Xid) mice. Int Arch Allergy Immunol 1996;111:118–125.
  63. Kawakami Y, Miura T, Bissonnette R, Hata D, Khan WN, Kitamura T, Maeda-Yamamoto M, Hartman SE, Yao L, Alt FW, Kawakami T: Bruton’s tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. Proc Natl Acad Sci USA 1997;94:3938–3942.
  64. Hata D, Kitaura J, Hartman SE, Kawakami Y, Yokota T, Kawakami T: Bruton’s tyrosine kinase-mediated interleukin-2 gene activation in mast cells. Dependence on the c-Jun N-terminal kinase activation pathway. J Biol Chem 1998;273:10979–10987.
  65. Kitaura J, Asai K, Maeda-Yamamoto M, Kawakami Y, Kikkawa U, Kawakami T: Akt-dependent cytokine production in mast cells. J Exp Med 2000;192:729–740.
  66. Jackson SP, Nesbitt WS, Kulkarni S: Signaling events underlying thrombus formation. J Thromb Haemost 2003;1:1602–1612.
  67. Nieswandt B, Watson SP: Platelet-collagen interaction: Is GPVI the central receptor? Blood 2003;102:449–461.
  68. Melford SK, Turner M, Briddon SJ, Tybulewicz VL, Watson SP: Syk and Fyn are required by mouse megakaryocytes for the rise in intracellular calcium induced by a collagen-related peptide. J Biol Chem 1997;272:27539–27542.
  69. Ezumi Y, Shindoh K, Tsuji M, Takayama H: Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc receptor gamma chain complex on human platelets. J Exp Med 1998;188:267–276.
  70. Briddon SJ, Melford SK, Turner M, Tybulewicz V, Watson SP: Collagen mediates changes in intracellular calcium in primary mouse megakaryocytes through syk-dependent and -independent pathways. Blood 1999;93:3847–3855.
  71. Briddon SJ, Watson SP: Evidence for the involvement of p59fyn and p53/56lyn in collagen receptor signalling in human platelets. Biochem J 1999;338/1:203–209.
  72. Watson SP, Gibbins J: Collagen receptor signalling in platelets: Extending the role of the ITAM. Immunol Today 1998;19:260–264.
  73. Hamazaki Y, Kojima H, Mano H, Nagata Y, Todokoro K, Abe T, Nagasawa T: Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets. Oncogene 1998;16:2773–2779.
  74. Oda A, Ikeda Y, Ochs HD, Druker BJ, Ozaki K, Handa M, Ariga T, Sakiyama Y, Witte ON, Wahl MI: Rapid tyrosine phosphorylation and activation of Bruton’s tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking. Blood 2000;95:1663–1670.
  75. Atkinson BT, Ellmeier W, Watson SP: Tec regulates platelet activation by GPVI in the absence of Btk. Blood 2003;102:3592–3599.
  76. Laffargue M, Ragab-Thomas JM, Ragab A, Tuech J, Missy K, Monnereau L, Blank U, Plantavid M, Payrastre B, Raynal P, Chap H: Phosphoinositide 3-kinase and integrin signalling are involved in activation of Bruton tyrosine kinase in thrombin-stimulated platelets. FEBS Lett 1999;443:66–70.
  77. Pasquet JM, Quek L, Stevens C, Bobe R, Huber M, Duronio V, Krystal G, Watson SP: Phosphatidylinositol 3,4,5-trisphosphate regulates Ca(2+) entry via btk in platelets and megakaryocytes without increasing phospholipase C activity. EMBO J 2000;19:2793–2802.
  78. Gross BS, Wilde JI, Quek L, Chapel H, Nelson DL, Watson SP: Regulation and function of WASp in platelets by the collagen receptor, glycoprotein VI. Blood 1999;94:4166–4176.
  79. Oda A, Ochs HD, Druker BJ, Ozaki K, Watanabe C, Handa M, Miyakawa Y, Ikeda Y: Collagen induces tyrosine phosphorylation of Wiskott-Aldrich syndrome protein in human platelets. Blood 1998;92:1852–1858.
  80. Crosby D, Poole AW: Interaction of Bruton’s tyrosine kinase and protein kinase Ctheta in platelets. Cross-talk between tyrosine and serine/threonine kinases. J Biol Chem 2002;277:9958–9965.
  81. Mukhopadhyay S, Ramars AS, Dash D: Bruton’s tyrosine kinase associates with the actin-based cytoskeleton in activated platelets. J Cell Biochem 2001;81:659–665.
  82. Mukhopadhyay S, Ramars AS, Ochs HD, Dash D: Bruton’s tyrosine kinase is a substrate of calpain in human platelets. FEBS Lett 2001;505:37–41.
  83. Futatani T, Watanabe C, Baba Y, Tsukada S, Ochs HD: Bruton’s tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinaemia and carrier females. Br J Haematol 2001;114:141–149.
  84. Bobe R, Wilde JI, Maschberger P, Venkateswarlu K, Cullen PJ, Siess W, Watson SP: Phosphatidylinositol 3-kinase-dependent translocation of phospholipase Cgamma2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation. Blood 2001;97:678–684.
  85. Suzuki-Inoue K, Inoue O, Frampton J, Watson SP: Murine GPVI stimulates weak integrin activation in PLCgamma2–/– platelets: Involvement of PLCgamma1 and PI3-kinase. Blood 2003;102:1367–1373.
  86. Wu H, Liu X, Jaenisch R, Lodish HF: Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 1995;83:59–67.
  87. Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K: Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998;93:397–409.
  88. Flanagan JG, Chan DC, Leder P: Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell 1991;64:1025–1035.
  89. Kazama A, Mano H, Morishita Y, Mori S: High expression of the tec gene product in murine testicular germ cells and erythroblasts. Pathol Int 1996;46:341–347.
  90. van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Lowenberg B, von Lindern M: Stem cell factor induces phosphatidylinositol 3′-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood 2000;96:3406–3413.
  91. Whyatt D, Lindeboom F, Karis A, Ferreira R, Milot E, Hendriks R, de Bruijn M, Langeveld A, Gribnau J, Grosveld F, Philipsen S: An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature 2000;406:519–524.
  92. Schmidt U, van den Akker E, Parren-van Amelsvoort M, Litos G, de Bruijn M, Gutiérrez L, Hendriks RW, Ellmeier W, Löwenberg B, Beug H, von Lindern M: Btk is required for an efficient response to erythropoietin and for SCF-controlled protection against TRAIL in erythroid progenitors. J Exp Med 2004;199:785–795.
  93. Vassilev A, Ozer Z, Navara C, Mahajan S, Uckun FM: Bruton’s tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex. J Biol Chem 1999;274:1646–1656.
  94. Pan S, An P, Zhang R, He X, Yin G, Min W: Etk/Bmx as a tumor necrosis factor receptor type 2-specific kinase: Role in endothelial cell migration and angiogenesis. Mol Cell Biol 2002;22:7512–7513.
  95. Gordon S: Alternative activation of macrophages. Nat Rev Immunol 2003;3:23–35.
  96. Aderem A, Underhill DM: Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999;17:593–623.
  97. Nathan C, Shiloh MU: Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA 2000;97:8841–8848.
  98. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 1998;282:2085–2088.
  99. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ: Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001;194:863–869.
  100. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, Walch E, Wirth T, O’Neill LA: Bruton’s tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. J Biol Chem 2003;278:26258–26264.
  101. Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, Brint E, Dunne A, Gray P, Harte MT, McMurray D, Smith DE, Sims JE, Bird TA, O’Neill LA: Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 2001;413:78–83.
  102. Medzhitov R: Toll-like receptors and innate immunity. Nat Rev Immunol 2001;1:135–145.
  103. Mukhopadhyay S, Mohanty M, Mangla A, George A, Bal V, Rath S, Ravindran B: Macrophage effector functions controlled by Bruton’s tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance. J Immunol 2002;168:2914–2921.
  104. Zhang JS, Feng WG, Li CL, Wang XY, Chang ZL: NF-kappa B regulates the LPS-induced expression of interleukin 12 p40 in murine peritoneal macrophages: Roles of PKC, PKA, ERK, p38 MAPK, and proteasome. Cell Immunol 2000;204:38–45.

    External Resources

  105. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM: Rational design and synthesis of a novel anti- leukemic agent targeting Bruton’s tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta- hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem 1999;274:9587–9599.
  106. Petro JB, Rahman SM, Ballard DW, Khan WN: Bruton’s tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement. J Exp Med 2000;191:1745–1754.
  107. Petro JB, Khan WN: Phospholipase C-gamma 2 couples Bruton’s tyrosine kinase to the NF-kappaB signaling pathway in B lymphocytes. J Biol Chem 2001;276:1715–1719.
  108. Saijo K, Mecklenbrauker I, Santana A, Leitger M, Schmedt C, Tarakhovsky A: Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha. J Exp Med 2002;195:1647–1652.
  109. Amoras AL, Kanegane H, Miyawaki T, Vilela MM: Defective Fc-, CR1- and CR3-mediated monocyte phagocytosis and chemotaxis in common variable immunodeficiency and X-linked agammaglobulinemia patients. J Investig Allergol Clin Immunol 2003;13:181–188.
  110. Mukhopadhyay S, George A, Bal V, Ravindran B, Rath S: Bruton’s tyrosine kinase deficiency in macrophages inhibits nitric oxide generation leading to enhancement of IL-12 induction. J Immunol 1999;163:1786–1792.
  111. Mukhopadhyay S, Sahoo PK, George A, Bal V, Rath S, Ravindran B: Delayed clearance of filarial infection and enhanced Th1 immunity due to modulation of macrophage APC functions in xid mice. J Immunol 1999;163:875–883.
  112. Cicchetti G, Allen PG, Glogauer M: Chemotactic signaling pathways in neutrophils: From receptor to actin assembly. Crit Rev Oral Biol Med 2002;13:220–228.
  113. Burg ND, Pillinger MH: The neutrophil: Function and regulation in innate and humoral immunity. Clin Immunol 2001;99:7–17.
  114. Gilbert C, Levasseur S, Desaulniers P, Dusseault AA, Thibault N, Bourgoin SG, Naccache PH: Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. II. Effects of LFM-A13, a specific Btk inhibitor. J Immunol 2003;170:5235–5243.
  115. Saito K, Tolias KF, Saci A, Koon HB, Humphries LA, Scharenberg A, Rawlings DJ, Kinet JP, Carpenter CL: BTK regulates PtdIns-4,5-P2 synthesis: Importance for calcium signaling and PI3K activity. Immunity 2003;19:669–678.
  116. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.
  117. Kang SW, Wahl MI, Chu J, Kitaura J, Kawakami Y, Kato RM, Tabuchi R, Tarakhovsky A, Kawakami T, Turck CW, Witte ON, Rawlings DJ: PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization. EMBO J 2001;20:5692–5702.

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