Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1998 Jan 15;17(2):443–454. doi: 10.1093/emboj/17.2.443

CD66-mediated phagocytosis of Opa52 Neisseria gonorrhoeae requires a Src-like tyrosine kinase- and Rac1-dependent signalling pathway.

C R Hauck 1, T F Meyer 1, F Lang 1, E Gulbins 1
PMCID: PMC1170395  PMID: 9430636

Abstract

The interaction of Neisseria gonorrhoeae with human phagocytes is a hallmark of gonococcal infections. Recently, CD66 molecules have been characterized as receptors for Opa52-expressing gonococci on human neutrophils. Here we show that Opa52-expressing gonococci or Escherichia coli or F(ab) fragments directed against CD66, respectively, activate a signalling cascade from CD66 via Src-like protein tyrosine kinases, Rac1 and PAK to Jun-N-terminal kinase. The induced signal is distinct from Fcgamma-receptor-mediated signalling and is specific for Opa52, since piliated Opa- gonococci, commensal Neisseria cinerea or E.coli do not stimulate this signalling pathway. Inhibition of Src-like kinases or Rac1 prevents the uptake of Opa52 bacteria, demonstrating the crucial role of this signalling cascade for the opsonin-independent, Opa52/CD66-mediated phagocytosis of pathogenic Neisseria.

Full Text

The Full Text of this article is available as a PDF (510.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam T., Giry M., Boquet P., Sansonetti P. Rho-dependent membrane folding causes Shigella entry into epithelial cells. EMBO J. 1996 Jul 1;15(13):3315–3321. [PMC free article] [PubMed] [Google Scholar]
  2. Bagrodia S., Dérijard B., Davis R. J., Cerione R. A. Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem. 1995 Nov 24;270(47):27995–27998. doi: 10.1074/jbc.270.47.27995. [DOI] [PubMed] [Google Scholar]
  3. Beauchemin N., Kunath T., Robitaille J., Chow B., Turbide C., Daniels E., Veillette A. Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells. Oncogene. 1997 Feb 20;14(7):783–790. doi: 10.1038/sj.onc.1200888. [DOI] [PubMed] [Google Scholar]
  4. Benchimol S., Fuks A., Jothy S., Beauchemin N., Shirota K., Stanners C. P. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989 Apr 21;57(2):327–334. doi: 10.1016/0092-8674(89)90970-7. [DOI] [PubMed] [Google Scholar]
  5. Bessen D., Gotschlich E. C. Interactions of gonococci with HeLa cells: attachment, detachment, replication, penetration, and the role of protein II. Infect Immun. 1986 Oct;54(1):154–160. doi: 10.1128/iai.54.1.154-160.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bhat K. S., Gibbs C. P., Barrera O., Morrison S. G., Jähnig F., Stern A., Kupsch E. M., Meyer T. F., Swanson J. The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. Mol Microbiol. 1992 Apr;6(8):1073–1076. doi: 10.1111/j.1365-2958.1992.tb02172.x. [DOI] [PubMed] [Google Scholar]
  7. Binstadt B. A., Brumbaugh K. M., Dick C. J., Scharenberg A. M., Williams B. L., Colonna M., Lanier L. L., Kinet J. P., Abraham R. T., Leibson P. J. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity. 1996 Dec;5(6):629–638. doi: 10.1016/s1074-7613(00)80276-9. [DOI] [PubMed] [Google Scholar]
  8. Bliska J. B., Galán J. E., Falkow S. Signal transduction in the mammalian cell during bacterial attachment and entry. Cell. 1993 Jun 4;73(5):903–920. doi: 10.1016/0092-8674(93)90270-z. [DOI] [PubMed] [Google Scholar]
  9. Brandt E., Van Damme J., Flad H. D. Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III. Cytokine. 1991 Jul;3(4):311–321. doi: 10.1016/1043-4666(91)90499-4. [DOI] [PubMed] [Google Scholar]
  10. Brown D. The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr Opin Immunol. 1993 Jun;5(3):349–354. doi: 10.1016/0952-7915(93)90052-t. [DOI] [PubMed] [Google Scholar]
  11. Brümmer J., Neumaier M., Göpfert C., Wagener C. Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas. Oncogene. 1995 Oct 19;11(8):1649–1655. [PubMed] [Google Scholar]
  12. Chen L. M., Hobbie S., Galán J. E. Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses. Science. 1996 Dec 20;274(5295):2115–2118. doi: 10.1126/science.274.5295.2115. [DOI] [PubMed] [Google Scholar]
  13. Chen T., Belland R. J., Wilson J., Swanson J. Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate. J Exp Med. 1995 Aug 1;182(2):511–517. doi: 10.1084/jem.182.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chen T., Gotschlich E. C. CGM1a antigen of neutrophils, a receptor of gonococcal opacity proteins. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14851–14856. doi: 10.1073/pnas.93.25.14851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chen Y. R., Wang X., Templeton D., Davis R. J., Tan T. H. The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem. 1996 Dec 13;271(50):31929–31936. doi: 10.1074/jbc.271.50.31929. [DOI] [PubMed] [Google Scholar]
  16. Coso O. A., Chiariello M., Yu J. C., Teramoto H., Crespo P., Xu N., Miki T., Gutkind J. S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995 Jun 30;81(7):1137–1146. doi: 10.1016/s0092-8674(05)80018-2. [DOI] [PubMed] [Google Scholar]
  17. Crespo P., Schuebel K. E., Ostrom A. A., Gutkind J. S., Bustelo X. R. Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature. 1997 Jan 9;385(6612):169–172. doi: 10.1038/385169a0. [DOI] [PubMed] [Google Scholar]
  18. Davis W., Harrison P. T., Hutchinson M. J., Allen J. M. Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis. EMBO J. 1995 Feb 1;14(3):432–441. doi: 10.1002/j.1460-2075.1995.tb07019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dehio C., Prévost M. C., Sansonetti P. J. Invasion of epithelial cells by Shigella flexneri induces tyrosine phosphorylation of cortactin by a pp60c-src-mediated signalling pathway. EMBO J. 1995 Jun 1;14(11):2471–2482. doi: 10.1002/j.1460-2075.1995.tb07244.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Elkins C., Rest R. F. Monoclonal antibodies to outer membrane protein PII block interactions of Neisseria gonorrhoeae with human neutrophils. Infect Immun. 1990 Apr;58(4):1078–1084. doi: 10.1128/iai.58.4.1078-1084.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fischer S. H., Rest R. F. Gonococci possessing only certain P.II outer membrane proteins interact with human neutrophils. Infect Immun. 1988 Jun;56(6):1574–1579. doi: 10.1128/iai.56.6.1574-1579.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gray-Owen S. D., Dehio C., Haude A., Grunert F., Meyer T. F. CD66 carcinoembryonic antigens mediate interactions between Opa-expressing Neisseria gonorrhoeae and human polymorphonuclear phagocytes. EMBO J. 1997 Jun 16;16(12):3435–3445. doi: 10.1093/emboj/16.12.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Greenberg S., Chang P., Silverstein S. C. Tyrosine phosphorylation of the gamma subunit of Fc gamma receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis in macrophages. J Biol Chem. 1994 Feb 4;269(5):3897–3902. [PubMed] [Google Scholar]
  24. Greenberg S., Chang P., Wang D. C., Xavier R., Seed B. Clustered syk tyrosine kinase domains trigger phagocytosis. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1103–1107. doi: 10.1073/pnas.93.3.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Haas R., Schwarz H., Meyer T. F. Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9079–9083. doi: 10.1073/pnas.84.24.9079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hall A. Small GTP-binding proteins and the regulation of the actin cytoskeleton. Annu Rev Cell Biol. 1994;10:31–54. doi: 10.1146/annurev.cb.10.110194.000335. [DOI] [PubMed] [Google Scholar]
  27. Hauck C. R., Lorenzen D., Saas J., Meyer T. F. An in vitro-differentiated human cell line as a model system to study the interaction of Neisseria gonorrhoeae with phagocytic cells. Infect Immun. 1997 May;65(5):1863–1869. doi: 10.1128/iai.65.5.1863-1869.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hsieh J. T., Luo W., Song W., Wang Y., Kleinerman D. I., Van N. T., Lin S. H. Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. Cancer Res. 1995 Jan 1;55(1):190–197. [PubMed] [Google Scholar]
  29. Ichijo H., Nishida E., Irie K., ten Dijke P., Saitoh M., Moriguchi T., Takagi M., Matsumoto K., Miyazono K., Gotoh Y. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997 Jan 3;275(5296):90–94. doi: 10.1126/science.275.5296.90. [DOI] [PubMed] [Google Scholar]
  30. Isberg R. R., Leong J. M. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell. 1990 Mar 9;60(5):861–871. doi: 10.1016/0092-8674(90)90099-z. [DOI] [PubMed] [Google Scholar]
  31. Joneson T., McDonough M., Bar-Sagi D., Van Aelst L. RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase. Science. 1996 Nov 22;274(5291):1374–1376. doi: 10.1126/science.274.5291.1374. [DOI] [PubMed] [Google Scholar]
  32. Kefalas P., Brown T. R., Brickell P. M. Signalling by the p60c-src family of protein-tyrosine kinases. Int J Biochem Cell Biol. 1995 Jun;27(6):551–563. doi: 10.1016/1357-2725(95)00024-J. [DOI] [PubMed] [Google Scholar]
  33. Knepper B., Heuer I., Meyer T. F., van Putten J. P. Differential response of human monocytes to Neisseria gonorrhoeae variants expressing pili and opacity proteins. Infect Immun. 1997 Oct;65(10):4122–4129. doi: 10.1128/iai.65.10.4122-4129.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kunath T., Ordoñez-Garcia C., Turbide C., Beauchemin N. Inhibition of colonic tumor cell growth by biliary glycoprotein. Oncogene. 1995 Dec 7;11(11):2375–2382. [PubMed] [Google Scholar]
  35. Kupsch E. M., Knepper B., Kuroki T., Heuer I., Meyer T. F. Variable opacity (Opa) outer membrane proteins account for the cell tropisms displayed by Neisseria gonorrhoeae for human leukocytes and epithelial cells. EMBO J. 1993 Feb;12(2):641–650. doi: 10.1002/j.1460-2075.1993.tb05697.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kypta R. M., Goldberg Y., Ulug E. T., Courtneidge S. A. Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell. 1990 Aug 10;62(3):481–492. doi: 10.1016/0092-8674(90)90013-5. [DOI] [PubMed] [Google Scholar]
  37. Lamarche N., Tapon N., Stowers L., Burbelo P. D., Aspenström P., Bridges T., Chant J., Hall A. Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell. 1996 Nov 1;87(3):519–529. doi: 10.1016/s0092-8674(00)81371-9. [DOI] [PubMed] [Google Scholar]
  38. Ley T. J., Connolly N. L., Katamine S., Cheah M. S., Senior R. M., Robbins K. C. Tissue-specific expression and developmental regulation of the human fgr proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):92–99. doi: 10.1128/mcb.9.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Makino S., van Putten J. P., Meyer T. F. Phase variation of the opacity outer membrane protein controls invasion by Neisseria gonorrhoeae into human epithelial cells. EMBO J. 1991 Jun;10(6):1307–1315. doi: 10.1002/j.1460-2075.1991.tb07649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Manser E., Leung T., Salihuddin H., Zhao Z. S., Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994 Jan 6;367(6458):40–46. doi: 10.1038/367040a0. [DOI] [PubMed] [Google Scholar]
  41. Martin G. A., Bollag G., McCormick F., Abo A. A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. EMBO J. 1995 May 1;14(9):1970–1978. doi: 10.1002/j.1460-2075.1995.tb07189.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Matsuda M., Park J. G., Wang D. C., Hunter S., Chien P., Schreiber A. D. Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides. Mol Biol Cell. 1996 Jul;7(7):1095–1106. doi: 10.1091/mbc.7.7.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Meyer T. F., Billyard E., Haas R., Storzbach S., So M. Pilus genes of Neisseria gonorrheae: chromosomal organization and DNA sequence. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6110–6114. doi: 10.1073/pnas.81.19.6110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Meyer T. F., Pohlner J., van Putten J. P. Biology of the pathogenic Neisseriae. Curr Top Microbiol Immunol. 1994;192:283–317. doi: 10.1007/978-3-642-78624-2_13. [DOI] [PubMed] [Google Scholar]
  45. Minden A., Lin A., Claret F. X., Abo A., Karin M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell. 1995 Jun 30;81(7):1147–1157. doi: 10.1016/s0092-8674(05)80019-4. [DOI] [PubMed] [Google Scholar]
  46. Ohta M., Furukawa Y., Ide C., Akiyama N., Utakoji T., Miura Y., Saito M. Establishment and characterization of four human monocytoid leukemia cell lines (JOSK-I, -S, -M and -K) with capabilities of monocyte-macrophage lineage differentiation and constitutive production of interleukin 1. Cancer Res. 1986 Jun;46(6):3067–3074. [PubMed] [Google Scholar]
  47. Oikawa S., Kuroki M., Matsuoka Y., Kosaki G., Nakazato H. Homotypic and heterotypic Ca(++)-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface. Biochem Biophys Res Commun. 1992 Jul 31;186(2):881–887. doi: 10.1016/0006-291x(92)90828-9. [DOI] [PubMed] [Google Scholar]
  48. Rest R. F., Shafer W. M. Interactions of Neisseria gonorrhoeae with human neutrophils. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S83–S91. doi: 10.1128/cmr.2.suppl.s83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Robertson B. D., Meyer T. F. Genetic variation in pathogenic bacteria. Trends Genet. 1992 Dec;8(12):422–427. doi: 10.1016/0168-9525(92)90325-x. [DOI] [PubMed] [Google Scholar]
  50. Rosenshine I., Ruschkowski S., Stein M., Reinscheid D. J., Mills S. D., Finlay B. B. A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation. EMBO J. 1996 Jun 3;15(11):2613–2624. [PMC free article] [PubMed] [Google Scholar]
  51. Rosette C., Karin M. Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science. 1996 Nov 15;274(5290):1194–1197. doi: 10.1126/science.274.5290.1194. [DOI] [PubMed] [Google Scholar]
  52. Salmon J. E., Brogle N. L., Edberg J. C., Kimberly R. P. Fc gamma receptor III induces actin polymerization in human neutrophils and primes phagocytosis mediated by Fc gamma receptor II. J Immunol. 1991 Feb 1;146(3):997–1004. [PubMed] [Google Scholar]
  53. Sells M. A., Knaus U. G., Bagrodia S., Ambrose D. M., Bokoch G. M., Chernoff J. Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol. 1997 Mar 1;7(3):202–210. doi: 10.1016/s0960-9822(97)70091-5. [DOI] [PubMed] [Google Scholar]
  54. Shafer W. M., Rest R. F. Interactions of gonococci with phagocytic cells. Annu Rev Microbiol. 1989;43:121–145. doi: 10.1146/annurev.mi.43.100189.001005. [DOI] [PubMed] [Google Scholar]
  55. Sheterline P., Rickard J. E., Richards R. C. Fc receptor-directed phagocytic stimuli induce transient actin assembly at an early stage of phagocytosis in neutrophil leukocytes. Eur J Cell Biol. 1984 May;34(1):80–87. [PubMed] [Google Scholar]
  56. Skubitz K. M., Campbell K. D., Ahmed K., Skubitz A. P. CD66 family members are associated with tyrosine kinase activity in human neutrophils. J Immunol. 1995 Dec 1;155(11):5382–5390. [PubMed] [Google Scholar]
  57. Stefanová I., Horejsí V., Ansotegui I. J., Knapp W., Stockinger H. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science. 1991 Nov 15;254(5034):1016–1019. doi: 10.1126/science.1719635. [DOI] [PubMed] [Google Scholar]
  58. Stern A., Brown M., Nickel P., Meyer T. F. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell. 1986 Oct 10;47(1):61–71. doi: 10.1016/0092-8674(86)90366-1. [DOI] [PubMed] [Google Scholar]
  59. Swanson J., Barrera O., Sola J., Boslego J. Expression of outer membrane protein II by gonococci in experimental gonorrhea. J Exp Med. 1988 Dec 1;168(6):2121–2129. doi: 10.1084/jem.168.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Swanson J., Sparks E., Young D., King G. Studies on Gonococcus infection. X. Pili and leukocyte association factor as mediators of interactions between gonococci and eukaryotic cells in vitro. Infect Immun. 1975 Jun;11(6):1352–1361. doi: 10.1128/iai.11.6.1352-1361.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Thompson J. A., Grunert F., Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal. 1991;5(5):344–366. doi: 10.1002/jcla.1860050510. [DOI] [PubMed] [Google Scholar]
  62. Twamley-Stein G. M., Pepperkok R., Ansorge W., Courtneidge S. A. The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7696–7700. doi: 10.1073/pnas.90.16.7696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Van Aelst L., Joneson T., Bar-Sagi D. Identification of a novel Rac1-interacting protein involved in membrane ruffling. EMBO J. 1996 Aug 1;15(15):3778–3786. [PMC free article] [PubMed] [Google Scholar]
  64. Verheij M., Bose R., Lin X. H., Yao B., Jarvis W. D., Grant S., Birrer M. J., Szabo E., Zon L. I., Kyriakis J. M. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature. 1996 Mar 7;380(6569):75–79. doi: 10.1038/380075a0. [DOI] [PubMed] [Google Scholar]
  65. Virji M., Heckels J. E. The effect of protein II and pili on the interaction of Neisseria gonorrhoeae with human polymorphonuclear leucocytes. J Gen Microbiol. 1986 Feb;132(2):503–512. doi: 10.1099/00221287-132-2-503. [DOI] [PubMed] [Google Scholar]
  66. Virji M., Makepeace K., Ferguson D. J., Watt S. M. Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae. Mol Microbiol. 1996 Dec;22(5):941–950. doi: 10.1046/j.1365-2958.1996.01551.x. [DOI] [PubMed] [Google Scholar]
  67. Wang A. V., Scholl P. R., Geha R. S. Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn. J Exp Med. 1994 Sep 1;180(3):1165–1170. doi: 10.1084/jem.180.3.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Watarai M., Kamata Y., Kozaki S., Sasakawa C. rho, a small GTP-binding protein, is essential for Shigella invasion of epithelial cells. J Exp Med. 1997 Jan 20;185(2):281–292. doi: 10.1084/jem.185.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Weel J. F., Hopman C. T., van Putten J. P. In situ expression and localization of Neisseria gonorrhoeae opacity proteins in infected epithelial cells: apparent role of Opa proteins in cellular invasion. J Exp Med. 1991 Jun 1;173(6):1395–1405. doi: 10.1084/jem.173.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Weinstein S. L., Gold M. R., DeFranco A. L. Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4148–4152. doi: 10.1073/pnas.88.10.4148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Xu Y., Potter J. W., Willman C. L. The function of src family tyrosine kinases in hematopoietic cells. Leuk Res. 1996 Mar;20(3):229–234. doi: 10.1016/0145-2126(95)00161-1. [DOI] [PubMed] [Google Scholar]
  72. Zheleznyak A., Brown E. J. Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C activation. Evidence for protein kinase C translocation to phagosomes. J Biol Chem. 1992 Jun 15;267(17):12042–12048. [PubMed] [Google Scholar]
  73. Ziegler S. F., Marth J. D., Lewis D. B., Perlmutter R. M. Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin. Mol Cell Biol. 1987 Jun;7(6):2276–2285. doi: 10.1128/mcb.7.6.2276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Zigmond S. H. Signal transduction and actin filament organization. Curr Opin Cell Biol. 1996 Feb;8(1):66–73. doi: 10.1016/s0955-0674(96)80050-0. [DOI] [PubMed] [Google Scholar]
  75. van Putten J. P., Paul S. M. Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells. EMBO J. 1995 May 15;14(10):2144–2154. doi: 10.1002/j.1460-2075.1995.tb07208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES