TYRO3 Protein Tyrosine Kinase (TYRO3)

Loss of function of the 3 TAM receptors, Tyro3, Axl, and Mer (MERTK), results in profound dysregulation of the immune response in mice (see ANIMAL MODEL). By analyzing TAM function in the dendritic cell subset of mouse antigen-presenting cells, Rothlin et al. (2007) found that TAM inhibited inflammation through an essential stimulator of inflammation, Ifnar, and its associated transcription factor, Stat1. Toll-like receptor (TLR) induction of Ifnar-Stat1 signaling upregulated the TAM system, which, in turn, induced the cytokine and TLR suppressors Socs1 and Socs3. Rothlin et al. (2007) concluded that cytokine-dependent activation of TAM signaling diverts a proinflammatory pathway to provide an instrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses.