ArticleMolecular biology of the cell2015
Ciliary transport regulates PDGF-AA/αα signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis.American journal of human genetics · 2021Pooled it
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Emerging principles of primary cilia dynamics in controlling tissue organization and function.The EMBO journal · 2023Review
- Primary cilia in hard tissue development and diseases.Frontiers of medicine · 2021Review
- Article
- An IFT20 mechanotrafficking axis is required for integrin recycling, focal adhesion dynamics, and polarized cell migration.Molecular biology of the cell · 2020Article
- Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models.Developmental cell · 2019Article
- Cellular signalling by primary cilia in development, organ function and disease.Nature reviews. Nephrology · 2019Review
- Sending mixed signals: Cilia-dependent signaling during development and disease.Developmental biology · 2019Review
- Ciliary signalling in cancer.Nature reviews. Cancer · 2018Review
- IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases.The Journal of cell biology · 2018Article
- Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.Developmental biology · 2017Article
- Primary Cilia and Coordination of Receptor Tyrosine Kinase (RTK) and Transforming Growth Factor β (TGF-β) Signaling.Cold Spring Harbor perspectives in biology · 2017Review
- Rab23 activities and human cancer-emerging connections and mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- The cilia-regulated proteasome and its role in the development of ciliopathies and cancer.Cilia · 2016Review
- Article
- Left-right asymmetry in the light of TOR: An update on what we know so far.Biology of the cell · 2015Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.