The DOI matches its Crossref record; 65 of the 67 references it cites were found in a registry or an index.
Rapid, Nongenomic Actions of Retinoic Acid on Phosphatidylinositol-3-Kinase Signaling Pathway Mediated by the Retinoic Acid Receptor
Open accessAbstract
Retinoic acid (RA) treatment of SH-SY5Y neuroblastoma cells results in activation of phosphatidylinositol-3-kinase (PI3K) signaling pathway, and this activation is required for RA-induced differentiation. Here we show that RA activates PI3K and ERK1/2 MAPK signaling pathways through a rapid, nongenomic mechanism that does not require new gene transcription or newly synthesized proteins. Activation of PI3K by RA appears to involve the classical nuclear receptor, retinoic acid receptor (RAR), on the basis of the pharmacological profile of the activation, loss, and gain of function experiments with mouse embryo fibroblast-RAR(alpha beta gamma)(L-/L-) null cells, and the physical association between liganded RAR and PI3K activity. The association of RAR with the two subunits of PI3K was differentially regulated by the ligand. Immunoprecipitation experiments performed in SH-SY5Y cells showed stable association between RARalpha and p85, the regulatory subunit of PI3K, independently of the presence of RA. In contrast, ligand administration increased the association of p110, the catalytic subunit of PI3K, to this complex. The intracellular localization of RAR proved to be relevant for PI3K activation. A chimerical RAR fusing c-Src myristylation domain to the N terminus of RARalpha (Myr-RARalpha) was targeted to plasma membrane. Transfection of Myr-RARalpha to mouse embryo fibroblast-RAR(alpha beta gamma)(L-/L-) null cells and COS-7 cells results in strong activation of the PI3K signaling pathway, although both in the absence as well in the presence of RA. Our results support a mechanism in which ligand binding to RAR would play a major role in the assembly and intracellular location of a signaling complex involving RAR and the subunits of PI3K.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Nevertheless, the RA-induced activation of the two MAPK pathways is subsequent to the activation of upstream cascades involving Rho-GTPases ( 114, 115, 117 ), phosphoinositide 3-kinase (PI3K) and/or protein kinase B (PKB)/Akt ( 120, 121, 123 ), suggesting an atypical, nongenomic activation event similar to that described for steroid nuclear receptors ( 124, 125 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [121]
In the citing paper
“However, in neuronal cells, the activation of Erks has been shown to involve either RAR ␣ localized in membranes ( 121 ) or RAR ␥ in association with the sarcome (Src) kinase ( 117 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [121]
In the citing paper
“However, in neuronal cells, Sertoli cells, and embryonic stem cells, RA instead activates the p42/p44 extracellular signal-regulated kinases (Erk) or classical MAPKs ( 116-122 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [121]
Citations
Cites
1 retracted
Sun, M., Yang, L., Feldman, R. I., Sun, X.-M., Bhalla, K. N., Jove, R., Nicosia, S. V., & Cheng, J. Q. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306295200 · Cited by 175
RetractedBrown, D. A., & Rose, J. K. (1992) · Cell · doi:10.1016/0092-8674(92)90189-j · Cited by 2,921
Production of high-titer helper-free retroviruses by transient transfection.
Pear, W. S., Nolan, G. P., Scott, M. L., & Baltimore, D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8392 · Cited by 2,267
Morgenstern, J. P., & Land, H. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.12.3587 · Cited by 2,099
Matthay, K. K., Villablanca, J. G., Seeger, R. C., Stram, D. O., Harris, R. E., Ramsay, N. K. C., Swift, P. S., Shimada, H., Black, C. T., Brodeur, G. M., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199910143411601 · Cited by 1,891
Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
Simoncini, T., Hafezi‐Moghadam, A., Brazil, D. P., Ley, K. F., Chin, W. W., & Liao, J. K. (2000) · Nature · doi:10.1038/35035131 · Cited by 1,436
Principles for modulation of the nuclear receptor superfamily
Gronemeyer, H., Gustafsson, J.-Å., & Laudet, V. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1551 · Cited by 1,285
Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J. F., & Waterfield, M. D. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.615 · Cited by 1,234
Nongenotropic, Sex-Nonspecific Signaling through the Estrogen or Androgen Receptors
Kousteni, S., Bellido, T., Plotkin, L. I., O’Brien, C. A., Bodenner, D., Li, H., Han, K., Gregorio, G. B. D., Katzenellenbogen, J. A., Katzenellenbogen, B. S., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00268-9 · Cited by 1,163
Razandi, M., Pedram, A., Greene, G. L., & Levin, E. R. (1999) · Molecular Endocrinology · doi:10.1210/mend.13.2.0239 · Cited by 1,075
Cited by
Sorted by citations
Retinoic acid receptors: From molecular mechanisms to cancer therapy
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., Lo-Coco, F., Ascenzi, P., & Nervi, C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.003 · Cited by 403
Vitamin A and retinoid signaling: genomic and nongenomic effects
Al Tanoury, Z., Piskunov, A., & Rochette-Egly, C. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r030833 · Cited by 408
Hall, J. A., Cannons, J. L., Grainger, J. R., dos Santos, L. M., Hand, T. W., Naik, S., Wohlfert, E. A., Chou, D. B., Oldenhove, G., Robinson, M., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.003 · Cited by 381
Retinoid pathway and cancer therapeutics
Bushue, N., & Wan, Y. Y. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.07.003 · Cited by 385
From carrot to clinic: an overview of the retinoic acid signaling pathway
Theodosiou, M., Laudet, V., & Schubert, M. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0268-z · Cited by 344
Metadata
- Authors
- Masiá, S., Alvarez, S., de Lera, A. R., & Barettino, D.
- Affiliations
- Biology of Hormone Action Unit (S.M., D.B.). Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia [Consejo Superior de Investigaciones Cientificas (CSIC)], E-46010 Valencia, Spain;
- Universidade de Vigo (S.A., A.R.d.L.), Departamento de Química Orgánica, Facultad de Ciencias, E-36200 Vigo, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Barettino, Domingo
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-10-01
- Volume
- 21
- Issue
- 10
- Pages
- 2391-2402
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2015219861
- Cited by
- 184
- References
- 67
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 16 · 2018: 12 · 2017: 5 · 2016: 13 · 2015: 11 · 2014: 16 · 2013: 15 · 2012: 11
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Funders
- European Commission
- Generalitat Valenciana
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- retinoic acid, non-genomic signaling, retinoic acid receptor, phosphatidylinositol 3-kinase, PI3K signaling, ERK signaling, neuronal differentiation, SH-SY5Y cells, p85 regulatory subunit, p110 catalytic subunit, RARα, subcellular localization
- MeSH terms
- Retinoic Acid Receptor alpha, Humans, Tretinoin, Signal Transduction, Receptors, Retinoic Acid, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Cell Line, Tumor, Mitogen-Activated Protein Kinase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
