K. Yamagata et al., RHEB, A GROWTH FACTOR-REGULATED AND SYNAPTIC ACTIVITY-REGULATED GENE,ENCODES A NOVEL RAS-RELATED PROTEIN, The Journal of biological chemistry, 269(23), 1994, pp. 16333-16339
Neuronal activity results in long term cellular changes that underlie
normal brain development and synaptic plasticity. To examine the molec
ular basis of activity-dependent plasticity, we have used differential
cloning techniques to identify genes that are rapidly induced in brai
n neurons by synaptic activity. Here we describe an inducible novel me
mber of the Ras family of small GTP-binding proteins we have termed Rh
eb. rheb mRNA is rapidly and transiently induced in hippocampal granul
e cells by seizures and by NMDA-dependent synaptic activity in the lon
g term potentiation paradigm. The predicted amino acid sequence of Rhe
b is most closely homologous to yeast Ras1 and human Rap2. The putativ
e GTP binding regions are highly conserved. A bacterial fusion protein
of Rheb binds GTP and exhibits intrinsic GTPase activity. Like Ha-Ras
, the carboxyl-terminal sequence encodes a CAAX box that is predicted
to signal post-translational farnesylation and to target Rheb to speci
fic membranes. rheb mRNA is expressed at comparatively high levels in
normal adult cortex as well as a number of peripheral tissues, includi
ng lung and intestine. In the developing brain, rheb mRNA is expressed
at relatively high levels in embryonic day 19 cortical plate, and exp
ression remains at stable levels throughout the remainder of prenatal
and postnatal development. Its close homology with ras and its rapid i
nducibility by receptor-dependent synaptic activity suggest that rheb
may play an important role in long term activity-dependent neuronal re
sponses.