The Function of lysyl-tRNA Synthetase and Ap4A as Signaling Regulators of MITF Activity in FcepsilonRI-activated Mast Cells

Immunity. 2004 Feb;20(2):145-51. doi: 10.1016/s1074-7613(04)00020-2.

Abstract

The involvement of microphthalmia transcription factor (MITF) in the function of mast cells, melanocytes, and osteoclasts has recently started to be investigated in depth. In a previous study, we found Hint to be associated with MITF in mast cells and showed that it suppresses MITF's transcriptional activity. Here, we have found that lysyl-tRNA synthetase (LysRS) is also associated with MITF and forms a multicomplex with MITF and Hint. We have also shown that Ap4A, an endogenous molecule consisting of two adenosine linked by four phosphate which is known to be synthesized by LysRS, is accumulated intracellularily above 700 microM in IgE-Ag-activated mast cells, binds to Hint, liberates MITF, and thus leads to the activation of MITF-dependent gene expression. This implies that LysRS plays a key role via Ap4A as an important signaling molecule in MITF transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism
  • Dinucleoside Phosphates / immunology*
  • Lysine-tRNA Ligase / immunology*
  • Lysine-tRNA Ligase / metabolism
  • Mast Cells / immunology*
  • Mice
  • Microphthalmia-Associated Transcription Factor
  • NIH 3T3 Cells
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection

Substances

  • DNA-Binding Proteins
  • Dinucleoside Phosphates
  • Hinterteil protein, Hydra vulgaris
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Receptors, IgE
  • Transcription Factors
  • diadenosine tetraphosphate
  • Protein-Tyrosine Kinases
  • Lysine-tRNA Ligase