Requirement for CD45 in fine-tuning mast cell responses mediated by different ligand-receptor systems

Cell Signal. 2009 Aug;21(8):1277-86. doi: 10.1016/j.cellsig.2009.03.018. Epub 2009 Mar 27.


The receptor-like protein tyrosine phosphatase CD45, the most abundant cell surface phosphatase on all nucleated hemopoietic cells, is a critical regulator of the activation status of Src family kinases (SFKs). To study the impact of CD45 on mast cell function, we compare bone marrow-derived mast cells (BMMCs) from CD45-deficient mice and from mice expressing an activating point mutation (E613R) in the juxtamembrane wedge of CD45. In response to Ag-triggered FcepsilonR1-mediated activation, CD45-deficient BMMCs exhibit increased inhibitory Lyn phosphorylation and drastically reduced effector functions (degranulation and cytokine secretion). In contrast, CD45 E613R BMMCs show stronger effector functions after Ag-triggering than wild-type (WT) BMMCs. Despite these dichotomous phenotypes, phosphorylation of the inhibitory tyrosine in the SFK Lyn of CD45 E613R BMMCs is comparable to CD45-deficient BMMCs. This unexpected phenotype most likely is due to attenuated interaction between CD45 E613R and Lyn and a hyper-activation of the Fyn-regulated phosphatidylinositol-3-kinase pathway. Interestingly, depending on the receptor system addressed, CD45-deficient and CD45 E613R BMMCs show uniform phenotypes as well. Proliferation of both cell types in response to IL-3 and/or SF is enhanced compared to WT BMMCs. Together, the data indicate that CD45 plays a complex and essential role in fine-tuning mast cell responses mediated by different ligand-receptor systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Degranulation
  • Cell Survival
  • Cells, Cultured
  • Immunoglobulin E / metabolism
  • Leukocyte Common Antigens / deficiency
  • Leukocyte Common Antigens / metabolism*
  • Mast Cells / enzymology*
  • Mast Cells / immunology
  • Mice
  • Mutant Proteins / metabolism
  • Phenotype
  • Phosphorylation
  • Proto-Oncogene Proteins c-fyn / metabolism
  • Receptors, IgE / metabolism
  • Signal Transduction
  • Silver / pharmacology
  • src-Family Kinases / metabolism


  • Mutant Proteins
  • Receptors, IgE
  • Immunoglobulin E
  • Silver
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases
  • Leukocyte Common Antigens