title: The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation.
abstract: BACKGROUND
  It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation.
  
  
  METHODS
  Human MC were stimulated by activated T cell membranes (T*m). Phosphorylation of kinases was assessed by Western blotting. Protein kinase D (PKD) translocation was visualized by confocal microscopy. Degranulation was assessed by β-hexosaminidase release and cytokine production by ELISA.
  
  
  RESULTS
  Stimulation of human MC by activated T*m resulted in the activation of PKD. PKD inhibition by the specific pharmacological inhibitor Gö6976 resulted in a reduction in the phosphorylation of p38 but not ERK. Gö6976 also inhibited degranulation and cytokine release.
  
  
  CONCLUSIONS
  MC stimulation by physical contact with T cells results in PKD activation, leading to the phosphorylation of p38, degranulation and release of cytokines. Understanding the molecular events associated with T cell-induced MC activation might lead to therapeutic approaches for controlling T cell-mediated inflammatory processes in which MC participate.
authors.affiliation: Laboratory of Allergy and Clinical Immunology, The Herbert Mast Cell Disorders Center, Meir Medical Center, Kfar Saba, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Pazit
authors.initials: P
authors.lastname: Salamon
authors.forename: Irit
authors.initials: I
authors.lastname: Shefler
authors.forename: Alon Y
authors.initials: AY
authors.lastname: Hershko
authors.forename: Yoseph A
authors.initials: YA
authors.lastname: Mekori
mesh_terms: D015550:Cell Degranulation / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016207:Cytokines; C089212:protein kinase D; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases