Putative model for TAM-mediated efferocytosis. The GLA domains of protein S and Gas6 bind to the phosphatidylserine-positive cell membrane of an apoptotic moiety. The SHBG domains bind to TAM receptors, which causes phosphorylation of the intracellular protein tyrosine kinase. Phosphorylated by the kinase, PI3K induces phosphorylation of PIP₂ to PIP₃, which facilitates phagocytosis. TAM receptor activation stimulates phospholipase Cγ2, leading to enhanced PKC activity. It has also been suggested that a Src family kinase is activated, resulting in recruitment of FAK, functionally cross-talking with αvβ5 integrin. It has also been suggested that a complex consisting of c-Src, PI3K, and STAT3 is established by Mer phosphorylation. This complex then inhibits inflammation in DCs. DAG, diacylglycerol; DC, dendritic cell; FAK, focal adhesion kinase; IP₃, inositol trisphosphate; MFGE8, milk fat globule-EGF factor 8; PIP₂, phosphatidylinositol (4,5)-bisphosphate; PIP₃, phosphatidylinositol (3,4,5)-triphosphate; PKC, protein kinase C; PLC, phospholipase C.