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

T N Stitt; G Conn; M Gore; C Lai; J Bruno; C Radziejewski; K Mattsson; J Fisher; D R Gies; P F Jones

doi:10.1016/0092-8674(95)90520-0

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.

Authors

T N Stitt¹, G Conn, M Gore, C Lai, J Bruno, C Radziejewski, K Mattsson, J Fisher, D R Gies, P F Jones, et al.

Affiliation

¹ Regeneron Pharmaceuticals, Incorporated, Tarrytown, New York 10591.

PMID: 7867073
DOI: 10.1016/0092-8674(95)90520-0

Abstract

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

Substances

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