Axl, Sky, and Mer are three members of a receptor tyrosine kinase (RTK) family that share a conserved intracellular tyrosine kinase domain and an extracellular domain similar to those seen in cell adhesion molecules. These RTKs bind the vitamin K-dependent protein growth-arrest-specific 6 (Gas6), which is structurally related to the protein S anticoagulation factor. Upon binding to its receptor, Gas6 activates phosphatidylinositol 3-kinase (PI3K) and its downstream targets Akt and S6K, as well as NF-κB. A large body of evidence supports a role for Gas6/Axl signaling in cell growth and survival in normal and cancer cells.