Striatum specific protein, Rhes regulates AKT pathway.
The Rhes/RASD2 GTPase complex is involved in dopamine D1/D2 receptor-mediated signaling and behavior. This GTP binding protein belongs to the RAS superfamily, along with Dexras1/RASD1, and is primarily expressed in the striatum. RASDs differ from typical small GTPases as they have an extended C-terminal tail of roughly 7 kDa. Previously, it has been shown that dopamine depletion reduces Rhes mRNA expression in the brain. Here we show that Rhes interacts with p85, the regulatory subunit of PI3K. Specifically, the C-terminal unique tail region of Rhes is responsible for this interaction. The interaction between p85 and the C-terminal region of Rhes is enhanced upon growth factor treatment in vitro, while AKT translocation to the membrane is facilitated in the presence of Rhes or the Rhes-p85 complex. These findings suggest that Rhes is a novel striatal regulator of the AKT-mediated pathway in the striatum.
Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 125 S 31st St., TRL Rm 2207, Philadelphia, PA 19104, United States.
Sookhee
S
Bang
Catherine
C
Steenstra
Sangwon F
SF
Kim
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection
D010982:Platelet-Derived Growth Factor; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D019204:GTP-Binding Proteins; C442475:Rasd2 protein, rat