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Title
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Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl.
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Authors
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M.R.Mark,
J.Chen,
R.G.Hammonds,
M.Sadick,
P.J.Godowsk.
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Ref.
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J Biol Chem, 1996,
271,
9785-9789.
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PubMed id
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Abstract
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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.
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