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Expression and functional effects of Eph receptor tyrosine kinase A family members on Langerhans like dendritic cells

By Else Munthe, Eivind Farmen Finne and Hans-Christian Aasheim

Abstract

BACKGROUND: The Eph receptors are the largest receptor tyrosine kinase family. Several family members are expressed in hematopoietic cells. Previously, the expression of a member of this family, EphA2, was identified on dendritic like cells in tonsils. We therefore specifically examined the expression of EphA2 on in vitro generated dendritic cells. RESULTS: In this study, expression of the EphA2 receptor was identified on in vitro generated Langerhans like dendritic cells compared to in vitro generated dendritic cells. We show that ligand induced engagement of the EphA2 receptor leads to receptor autophosphorylation indicating a functional receptor signaling pathway in these cells. We also observe phosphorylation and dephosphorylation of distinct proteins following ligand activation of EphA receptors. In co-stimulation assays, receptor-ligand interaction reduces the capacity of the Langerhans like dendritic cells to stimulate resting CD4+ T cells. CONCLUSION: Engagement of EphA receptor tyrosine kinases on Langerhans like dendritic cells induces signaling as shown by tyrosine phosphorylation and dephosphorylation of distinct proteins. Furthermore this engagement renders the cells less capable of stimulating CD4+ T cells

Topics: Research Article
Publisher: BioMed Central
Year: 2004
DOI identifier: 10.1186/1471-2172-5-9
OAI identifier: oai:pubmedcentral.nih.gov:443508
Provided by: PubMed Central

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Citations

  1. (1998). A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a Tkiller cell. Nature
  2. (2000). Aasheim H: Ephrin-B2 is a candidate ligand for the Eph receptor,
  3. (2000). Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol
  4. (2002). AG: Expression and function of the Eph A receptors and their ligands ephrins A in the rat thymus.
  5. (2001). An ephrinA-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120 kDa protein.
  6. (1997). Committee: Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell
  7. (2002). Complementary dendritic cell-activating function of CD8+ and CD4+ T cells: helper role of CD8+ T cells in the development of T helper type 1 responses.
  8. (2001). Cross-Linking of
  9. (1999). D: CD34+ cell-derived CD14+ precursor cells develop into Langerhans cells in a TGF-beta 1-dependent manner.
  10. (2001). Danger signals: SOS to the immune system. Curr Opin Immunol
  11. (1995). DC: Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression. Cancer Res
  12. (1999). DC: Up-regulation of ephrin-A1 during melanoma progression.
  13. (2002). Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis. Microsc Res Tech
  14. (1995). Dixit VM: Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase.
  15. (2000). E: Dendritic cell activation by danger and antigen-specific T-cell signalling. Exp Dermatol
  16. (1996). Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron
  17. (2002). EphB6 crosslinking results in costimulation of T cells.
  18. (2000). Expression of Eph receptors and ephrins is differentially regulated by E-cadherin.
  19. (1998). Hermine O: Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells.
  20. (2004). Human dendritic cells express neuronal Eph receptor tyrosine kinases: role of EphA2 in regulating adhesion to fibronectin. Blood
  21. (2001). Lineage commitment in lymphocytes: controlling the immune response.
  22. (2000). Logtenberg T: A splice variant of human ephrin-A4 encodes a soluble molecule that is secreted by activated human B lymphocytes. Blood
  23. (2002). Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol
  24. (1998). Melief CJ: Tcell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature
  25. (1999). MS: E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. Cell Growth Differ
  26. (2002). Onoe K: Activation of extracellular signal-related kinase by TNF-alpha controls the maturation and function of murine dendritic cells.
  27. (2000). Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol
  28. (1996). Pawson T: Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature
  29. (1997). RG: Tyrosine kinase receptors concentrated in caveolae-like domains from neuronal plasma membrane.
  30. (2000). Robbins SM: Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner.
  31. (1999). Ruoslahti E: An Eph receptor regulates integrin activity through R-Ras.
  32. (2001). Sallusto F: Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol
  33. (2000). Sallusto F: Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science
  34. (1998). Signaling by Eph receptors and their ephrin ligands. Curr Opin Neurobiol
  35. (2001). Signals from Eph and ephrin proteins: a developmental tool kit. Sci STKE
  36. (2000). Skolnik EY: Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation. Mol Cell Biol
  37. (1999). SM: Compartmentalized signaling by GPIanchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion. Genes Dev
  38. (1990). T: cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases. Mol Cell Biol
  39. (2001). The dendritic cell cytoskeleton is critical for the formation of the immunological synapse.
  40. (1998). TO: Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev
  41. (1999). TO: Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins.
  42. (1997). TRANCE (tumor necrosis factor [TNF]-related activationinduced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med
  43. (1997). Tyrosine phosphorylation of transmembrane ligands for Eph receptors. Science
  44. (1999). Udey MC: Epidermal Langerhans cells: from neurons to nature's adjuvants. Adv Dermatol
  45. (1998). WR: Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature
  46. (2001). Zipursky SL: Signaling downstream of Eph receptors and ephrin ligands. Cell

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