TAM family receptor tyrosine kinases (TAM) (TAM)

The TAM family consists of three receptor tyrosine kinases: Tyro3, Axl, and MerTK, which are essential for maintaining tissue homeostasis [1: Lemke, G. (2013). Nat Rev Immunol]. These receptors are activated by ligands such as Gas6 and Protein S, which bridge the receptors to phosphatidylserine on apoptotic cells, facilitating their clearance via efferocytosis [2: Rothlin, C. V., et al. (2015). Annu Rev Immunol]. Beyond homeostasis, TAM signaling acts as a critical negative feedback loop for the innate immune system by inhibiting Toll-like receptor and cytokine receptor signaling [3: Lemke, G. (2019). Cold Spring Harb Perspect Biol]. In many cancers, TAM receptors are overexpressed or overactivated, promoting tumor cell survival, invasion, and immune evasion within the tumor microenvironment [4: Graham, D. K., et al. (2014). Nat Rev Cancer]. They also serve as entry factors for several enveloped viruses, including Zika and Ebola, through a process called apoptotic mimicry [5: Meertens, L., et al. (2012). Cell Host Microbe]. Consequently, TAM kinases have emerged as significant therapeutic targets, with several small-molecule inhibitors and monoclonal antibodies currently in clinical development to treat malignancies and potentially viral infections [6: Akalu, Y. T., et al. (2017). Immunol Rev].

Other names

Tyro3, Axl, and MerTK familyTAM receptorsTAM subfamily of RTKs

Small molecule inhibition of the intracellular kinase domain (ATP-competitive) and monoclonal antibody-mediated blockade of ligand binding or receptor dimerization.