The impact of the TAM family of receptor protein tyrosine kinases (RTKs) on physiology recently gained momentum, as they play pivotal roles in several physiological systems. TYRO3, AXL and MERTK comprise the TAM family of RTKs, and together with their cognate ligands Growth Arrest-Specific 6 (GAS6) and Protein S (PROS1) mediate various molecular signaling pathways and cellular functions, mostly impacting adult tissues. All receptors share a similar domain structure. The extracellular domain is comprised of two immunoglobulin (Ig) type domains at the amino-most terminus. Two fibronectin type III domains are located adjacent to the transmembrane domain. Their kinase domain resides intracellularly, mediating various intracellular pathways, including PI3K/AKT, ERK/MAPK and JAK/STAT. The two chief functions mediated by TAM receptors in adult tissues are the phagocytic uptake of membranes and apoptotic cells, and negative regulation of the immune response.  It should be mentioned that the overexpression and upregulation of TAMs is recognized in various human cancers, where activated TAM signaling functionally supports increased proliferation, migration, invasion, enhanced tumor cell survival, angiogenesis and promotes resistance to chemotherapeutic drugs.

References

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