Collaboration work with Scripps and Hebrew University was introduced in JACI.

Phosphorylation triggers the structural and functional switch of a housekeeping protein for mast cells 

Cross-linking of IgE receptors on the surfaces of mast cells results in the synthesis of a number of mediators that is regulated by the transcription factor microphthalmia-associated transcription factor (MITF). Activation of MITF requires the production of the antigen-IgE–induced second messenger diadenosine tetraphosphate (Ap₄A). Prior studies have demonstrated a role for lysyl-tRNA synthetase (LysRS), an aminoacyl tRNA synthetase that catalyzes the assignment of lysine to a tRNA as part of the fundamental machinery in protein translation in MITF activation, but the mechanism for regulation of these 2 distinct functions for LysRS is unknown. Studies performed by Ofir-Birin et al (Mol Cell 2013;49:30-42) delineate a cascade of events triggered by phosphorylation of LysRS after activation of the IgE receptor that leads to a strong conformational change, followed by translocation of LysRS from the cytoplasm to the nucleus, where it binds to MITF and generates Ap₄A to activate transcription of MITF target genes (see video available at https://www.dropbox.com/s/1xh5p3apnuzc5y2/13_11_12_hadasa.wmv). Their findings establish a unique switch mechanism using housekeeping proteins for prompt induction of inflammatory mediators by activated mast cells.

We asked authors Ehud Razin from the Institute for Medical Research Israel-Canada/Hebrew University–Hadassah Medical School and Min Guo from the Scripps Research Institute to comment on the significance of these results: “This will allow [us] to obtain a unique insight regarding the physiological significance of the second messenger, Ap₄A, in mast cell function and in allergic related diseases.”