The function of Lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcεRI-activated mast cells

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 APA an endogenous molecule consisting of two adenosine linked by four phosphate which is known to be synthesized by LysRS, is accumulated intracellularily above 700 muM 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 Ap(4)A as an important signaling molecule in MITF transcriptional activity.