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• W2167490493 abstract "Primary cilia are built and maintained by intraflagellar transport (IFT), whereby the two IFT complexes, IFTA and IFTB, carry cargo via kinesin and dynein motors for anterograde and retrograde transport, respectively. Many signaling pathways, including platelet- derived growth factor (PDGF)-AA/αα, are linked to primary cilia. Active PDGF-AA/αα signaling results in phosphorylation of Akt at two residues: P-Akt T308 and P-Akt S473 , and previous work showed decreased P-Akt S473 in response to PDGF-AA upon anterograde transport disruption. In this study, we investigated PDGF-AA/αα signaling via P-Akt T308 and P-Akt S473 in distinct ciliary transport mutants. We found increased Akt phosphorylation in the absence of PDGF-AA stimulation, which we show is due to impaired dephosphorylation resulting from diminished PP2A activity toward P-Akt T308 . Anterograde transport mutants display low platelet-derived growth factor receptor (PDGFR)α levels, whereas retrograde mutants exhibit normal PDGFRα levels. Despite this, neither shows an increase in P-Akt S473 or P-Akt T308 upon PDGF-AA stimulation. Because mammalian target of rapamycin complex 1 (mTORC1) signaling is increased in ciliary transport mutant cells and mTOR signaling inhibits PDGFRα levels, we demonstrate that inhibition of mTORC1 rescues PDGFRα levels as well as PDGF-AA–dependent phosphorylation of Akt S473 and Akt T308 in ciliary transport mutant MEFs. Taken together, our data indicate that the regulation of mTORC1 signaling and PP2A activity by ciliary transport plays key roles in PDGF-AA/αα signaling." @default.
• W2167490493 created "2016-06-24" @default.
• W2167490493 creator A5013638496 @default.
• W2167490493 creator A5048006952 @default.
• W2167490493 date "2015-01-15" @default.
• W2167490493 modified "2023-10-03" @default.
• W2167490493 title "Ciliary transport regulates PDGF-AA/αα signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity" @default.
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• W2167490493 doi "https://doi.org/10.1091/mbc.e14-05-0952" @default.
• W2167490493 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4294681" @default.
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• W2167490493 hasPublicationYear "2015" @default.
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