THE ANTICOAGULATION FACTOR PROTEIN-S AND ITS RELATIVE, GAS6, ARE LIGANDS FOR THE TYRO 3 AXL FAMILY OF RECEPTOR TYROSINE KINASES/

We report the identification of ligands for Tyro 3 (alternatively call ed Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. Thes e ligands correspond to protein S, a protease regulator that is a pote nt anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings th at the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracel lular signaling via a G protein-coupled cell surface receptor. Proteas es and protease regulators that also activate specific cell surface re ceptors may serve to integrate coagulation with associated cellular re sponses required for tissue repair and growth, as well as to coordinat e protease cascades and associated cellular responses in other systems , such as those involved in growth and remodeling of the nervous syste m.