A partial cDNA encoding a novel putative p2, ras guanine nucleotide re
lease-inducing factor (GRF), GRF2, was amplified from murine embryonic
stem cells. The presumptive catalytic region of GRF2 is related to th
e yeast Ras GRF encoded by CDC25. GRF2 is 80% identical to murine CDC2
5Mm/ras-GRF, but is more similar to yeast CDC25 than to other ras GRFs
related to the Drosophila son of sevenless gene product. A 9-kb GRF2
messenger RNA was highly expressed in brain, but GRF2-specific antibod
ies recognized apparent GRF2 proteins in various mouse tissues in addi
tion to brain. Thus GRF2 represents a novel widely-expressed protein t
hat is highly related to CDC25Mm/ras-GRF, at least in its catalytic do
main. Both GRF2 and CDC25Mm/ras-GRF are expressed in murine embryonic
stem cells, suggesting that different Ras activators may regulate ras-
dependent proliferation and differentiation in early mouse development
. (C) 1993 Wiley-Liss, Inc.