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Updated: Apr 23, 2026

Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors GPCRs
Published on: February 5, 2022
Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities
Erin D Lew1, Jennifer Oh1, Patrick G Burrola1
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
Abstract:
The TAM receptor tyrosine kinases Tyro3, Axl, and Mer regulate key features of cellular physiology, yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood. We have used biochemical and genetic analyses to delineate the rules for TAM receptor-ligand engagement and find that the TAMs segregate into two groups based on ligand specificity, regulation by phosphatidylserine, and function. Tyro3 and Mer are activated by both ligands but only Gas6 activates Axl. Optimal TAM signaling requires coincident TAM ligand engagement of both its receptor and the phospholipid phosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is significantly weakened as a Tyro3/Mer agonist and is inert as an Axl agonist, even though it binds to Axl with wild-type affinity. In two settings of TAM-dependent homeostatic phagocytosis, Mer plays a predominant role while Axl is dispensable, and activation of Mer by Protein S is sufficient to drive phagocytosis.
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