The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases

Cell. 1995 Feb 24;80(4):661-70. doi: 10.1016/0092-8674(95)90520-0.


We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Astrocytes / metabolism
  • Axl Receptor Tyrosine Kinase
  • Blotting, Northern
  • Cell Division
  • Chromatography, Affinity
  • Gene Expression Regulation
  • Intercellular Signaling Peptides and Proteins*
  • Ligands
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein S / genetics
  • Protein S / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins
  • RNA, Messenger / analysis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Schwann Cells / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Oncogene Proteins
  • Protein S
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • growth arrest-specific protein 6
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human
  • Axl Receptor Tyrosine Kinase
  • AXL receptor tyrosine kinase, mouse