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Vol. 273, Issue 3, 1782-1787, January 16, 1998
From The Scripps Research Institute,
La Jolla, California 92037
Human cells contain four homologous Ras proteins,
but it is unknown whether these homologues have different biological
functions. As a first step in determining if Ras homologues might
participate in distinct signaling cascades, we assessed whether a given
Ras guanine nucleotide exchange factor could selectively activate a
single Ras homologue in vivo. We found that
Ras-GRF/Cdc25Mm activates Ha-Ras, but does not activate
N-Ras or K-Ras 4B, protein in vivo. Moreover, our results
suggested that residues within the C-terminal hypervariable domains of
Ras proteins may dictate, at least in part, the specificity of
Ras-GRF/CDC25Mm for Ha-Ras protein. Our studies represent
the first biochemical evidence that a Ras GEF can selectively activate
a single Ras homologue in vivo. Selective activation of a
single Ras homologue by Ras-GRF/Cdc25Mm or other Ras
guanine nucleotide exchange factors could potentially enable each of
the Ras homologues to participate in different signal transduction
pathways.
Ras-GRF Activates Ha-Ras, but Not N-Ras or K-Ras 4B, Protein
in Vivo
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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