Figure 1.

TAM receptor activation by Gas6, Pros1, and PS-positive apoptotic cells. TAM receptors exhibit differential activation by their ligands, Gas6 and Pros1. While Gas6 preferentially activates Axl and to lesser extent Tyro3 and Mertk; Pros1 does not activate Axl and is specific for Mertk and Tyro3. However, in the presence of externalized phosphatidylserine (PS) on the surface of apoptotic cells, stressed tumor vasculature, or PS- positive tumor exosomes, Gas6 and Pros1 mediated activation of TAMs is enhanced. After ligand binding, TAMs undergo subsequent dimerization and auto-phosphorylation of catalytic tyrosine kinase domain leading to downstream effector pathways.