rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein

Kanato Yamagata, Laura K. Sanders, Walter E. Kaufmann, Wendy Yee, Carol A Barnes, Daniel Nathans, Paul F. Worley

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Neuronal activity results in long term cellular changes that underlie normal brain development and synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here we describe an inducible novel member of the Ras family of small GTP-binding proteins we have termed Rheb. rheb mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent synaptic activity in the long term potentiation paradigm. The predicted amino acid sequence of Rheb is most closely homologous to yeast Ras1 and human Rap2. The putative 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 specific membranes, rheb mRNA is expressed at comparatively high levels in normal adult cortex as well as a number of peripheral tissues, including lung and intestine. In the developing brain, rheb mRNA is expressed at relatively high levels in embryonic day 19 cortical plate, and expression remains at stable levels throughout the remainder of prenatal and postnatal development. Its close homology with ras and its rapid inducibility by receptor-dependent synaptic activity suggest that rheb may play an important role in long term activity-dependent neuronal responses.

Original languageEnglish (US)
Pages (from-to)16333-16339
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number23
StatePublished - Jun 10 1994

Fingerprint

ras Proteins
Brain
Intercellular Signaling Peptides and Proteins
Genes
Guanosine Triphosphate
Messenger RNA
Plasticity
Prenylation
Proteins
Neurotransmitter Receptor
Neuronal Plasticity
Bacterial Proteins
Long-Term Potentiation
Cloning
GTP Phosphohydrolases
N-Methylaspartate
GTP-Binding Proteins
Cerebral Cortex
Yeast
Neurons

ASJC Scopus subject areas

  • Biochemistry

Cite this

Yamagata, K., Sanders, L. K., Kaufmann, W. E., Yee, W., Barnes, C. A., Nathans, D., & Worley, P. F. (1994). rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein. Journal of Biological Chemistry, 269(23), 16333-16339.

rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein. / Yamagata, Kanato; Sanders, Laura K.; Kaufmann, Walter E.; Yee, Wendy; Barnes, Carol A; Nathans, Daniel; Worley, Paul F.

In: Journal of Biological Chemistry, Vol. 269, No. 23, 10.06.1994, p. 16333-16339.

Research output: Contribution to journalArticle

Yamagata, K, Sanders, LK, Kaufmann, WE, Yee, W, Barnes, CA, Nathans, D & Worley, PF 1994, 'rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein', Journal of Biological Chemistry, vol. 269, no. 23, pp. 16333-16339.
Yamagata K, Sanders LK, Kaufmann WE, Yee W, Barnes CA, Nathans D et al. rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein. Journal of Biological Chemistry. 1994 Jun 10;269(23):16333-16339.
Yamagata, Kanato ; Sanders, Laura K. ; Kaufmann, Walter E. ; Yee, Wendy ; Barnes, Carol A ; Nathans, Daniel ; Worley, Paul F. / rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel ras-related protein. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 23. pp. 16333-16339.
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