RGD Reference Report - PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways. - Rat Genome Database

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PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways.

Authors: Xiong, X  Xie, R  Zhang, H  Gu, L  Xie, W  Cheng, M  Jian, Z  Kovacina, K  Zhao, H 
Citation: Xiong X, etal., Neurobiol Dis. 2014 Jun;66:43-52. doi: 10.1016/j.nbd.2014.02.006. Epub 2014 Feb 27.
RGD ID: 10040971
Pubmed: PMID:24583056   (View Abstract at PubMed)
PMCID: PMC4448971   (View Article at PubMed Central)
DOI: DOI:10.1016/j.nbd.2014.02.006   (Journal Full-text)

The proline-rich Akt substrate of 40kDa (PRAS40) protein is not only a substrate of the protein kinase Akt but also a component of the mTOR complex 1 (mTORC1), thus it links the Akt and the mTOR pathways. We investigated the potential protective role of PRAS40 in cerebral ischemia and its underlying mechanisms by using rats with lentiviral over-expression of PRAS40 and mice with PRAS40 gene knockout (PRAS40 KO). Our results show that gene transfer of PRAS40 reduced infarction size in rats by promoting phosphorylation of Akt, FKHR (FOXO1), PRAS40, and mTOR. In contrast, PRAS40 KO increased infarction size. Although the PRAS40 KO under normal condition did not alter baseline levels of phosphorylated proteins in the Akt and mTOR pathways, PRAS40 KO that underwent stroke exhibited reduced protein levels of p-S6K and p-S6 in the mTOR pathway but not p-Akt, or p-PTEN in the Akt pathway. Furthermore, co-immunoprecipitation suggests that there were less interactive effects between Akt and mTOR in the PRAS40 KO. In conclusion, PRAS40 appears to reduce brain injury by converting cell signaling from Akt to mTOR.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
middle cerebral artery infarction  ISOMtor (Rattus norvegicus)10040971; 10040971 RGD 
middle cerebral artery infarction  IEP 10040971 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPIMtor (Rattus norvegicus)10040971 RGD 
protein kinase binding  IPIAkt1 (Rattus norvegicus)10040971 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information