Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl.

Rse, Ax1, and c-Mer comprise a family of cell adhesion molecule-related tyrosine kinase receptors. Human Gas6 was recently shown to act as a ligand for both human Rse (Godowski et al., 1995) and human Ax1 (Varnum et al., 1995). Gas6 contains an NH2-terminal Gla domain followed by four epidermal growth ...
factor-like repeats and tandem globular (G) domains. The G domains are related to those found in sex hormone-binding globulin and to those utilized by laminin and agrin for binding to the dystroglycan complex. A series of Gas6 variants were tested for their ability to bind to Rse and Ax1. The Gla domain and epidermal growth factor-like repeats were not required for receptor binding, as deletion variants of Gas6 which lacked these domains bound to the extracellular domains of both Rse and Axl. A deletion variant of Gas6 containing just the G domain region was shown to activate Rse phosphorylation. These results provide evidence that G domains can act as signaling molecules by activating transmembrane receptor tyrosine kinases. Furthermore, they provide a structural link between the activation of cell adhesion related receptors and the control of cell growth and differentiation by the G domain-containing superfamily of proteins.
Mesh Terms:
Base Sequence, Binding Sites, Brain, Cell Line, DNA Primers, Genetic Variation, Humans, Intercellular Signaling Peptides and Proteins, Kidney, Kinetics, Ligands, Liver, Molecular Sequence Data, Mutagenesis, Mutagenesis, Site-Directed, Oncogene Proteins, Polymerase Chain Reaction, Protein Biosynthesis, Proteins, Receptor Protein-Tyrosine Kinases, Recombinant Proteins, Sequence Deletion, Sequence Tagged Sites, Transfection
J. Biol. Chem.
Date: Apr. 19, 1996
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