The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Regulation of Phosphorylation of Thr-308 of Akt, Cell Proliferation, and Survival by the B55α Regulatory Subunit Targeting of the Protein Phosphatase 2A Holoenzyme to Akt
Open accessAbstract
Akt is a protein serine/threonine kinase that is involved in the regulation of diverse cellular processes. Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural subunit (A), catalytic subunit (C), and a variable regulatory subunit (B). Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells. Akt was shown to associate with ectopically expressed B55alpha subunit in NIH3T3 cells. The direct interaction between B55alpha subunit and Akt was confirmed using in vitro pulldown analyses. Intriguingly, we found that overexpression of B55alpha subunit significantly impaired phosphorylation at Thr-308, but to a lesser extent at Ser-473 of Akt in both FL5.12 and NIH3T3 cells. Concomitantly, phosphorylation of a subset of Akt substrates, including FoxO3a, was substantially decreased by B55alpha overexpression in these cells. Silencing of B55alpha expression markedly increased phosphorylation at Thr-308 but not at Ser-473 in both FL5.12 cells and NIH3T3 cells. Consistently, PP2A AB55alphaC holoenzymes preferentially dephosphorylated phospho-Thr-308 rather than phospho-Ser-473 in in vitro dephosphorylation assays. Furthermore, B55alpha overexpression retarded proliferation of NIH3T3 cells, and knockdown of B55alpha expression increased survival of FL5.12 cells upon interleukin-3 deprivation. Together, our data demonstrate that B55alpha-dependent targeting of the PP2A holoenzyme to Akt selectively regulates Akt phosphorylation at Thr-308 to regulate cell proliferation and survival.
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
“Consistently, an in vitro dephosphorylation assay showed that PP2A/B55α dephosphorylates AKT on Thr308 preferentially over Ser473, suggesting that B55α selectively and directly regulates AKT phosphorylation on Thr308 (Kuo et al., 2008).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Kuo et al., 2008
In the citing paper
“In the PI3K/AKT pathway, both PI3K and AKT downstream signaling factors are substrates of PP2A (Kuo et al., 2008; Petritsch et al., 2000).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Kuo et al., 2008
Citations
Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,155
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216
Maehama, T., & Dixon, J. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13375 · Cited by 3,104
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 3,014
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery
Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., & Mills, G. B. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1902 · Cited by 2,214
Janssens, V., & Goris, J. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3530417 · Cited by 1,927
The protein kinase B/Akt signalling pathway in human malignancy
Nicholson, K. M., & Anderson, N. G. (2002) · Cellular Signalling · doi:10.1016/s0898-6568(01)00271-6 · Cited by 1,665
Research works printed but not linked: 3
- Bellacosa, 1991, Science, 254, 274
- Healy, 1991, Mol. Cell. Biol., 11, 5767
- Liu, 2004, Am. J. Physiol., 286, H2204
Cited by
Sorted by citations
Items 301–372 of 372
Modulation of PP2A activity by Jacalin: is it through caveolae and ER chaperones?
Ahmed, N., Pany, S., Rahman, M. A., Srivastava, S. S., Sneh, A., & Krishnasastry, M. V. (2009) · Glycoconjugate Journal · doi:10.1007/s10719-009-9258-5 · Cited by 5
Menna, L. D., Orlando, R., D’Errico, G., Ginerete, R. P., Machaczka, A., Bonaccorso, C. M., Arena, A., Spatuzza, M., Celli, R., Alborghetti, M., et al. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109642 · Cited by 5
Zhao, J., Chen, G., Li, J., Liu, S., Jin, Q., Zhang, Z., Qi, F., Zhang, J., & Xu, J. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01796-0 · Cited by 5
Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors
Hidai, C., Kitano, H., Ishikawa, T., Mamiya, A., Egoshi, K., & Kokubun, S. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s90801 · Cited by 5
Unraveling the molecular complexity of bicuspid aortopathy: Lessons from comparative proteomics
Pozo‐Vilumbrales, B., Martín-Chaves, L., López-Unzu, M. Á., Soto‐Navarrete, M. T., Pavón, F. J., Rodríguez‐Capitán, J., & Fernández, B. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167679 · Cited by 4
Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways
Hernández-González, K. D., Vinchira-Lamprea, M. A., Hernández-Aranda, J., & Olivares-Reyes, J. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157434 · Cited by 4
PP2A Affects Angiogenesis via Its Interaction with a Novel Phosphorylation Site of TSP1
Thalwieser, Z., Fonódi, M., Király, N., Csoŕtos, C., & Boratkó, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031844 · Cited by 4
Cailliau, K., Lescuyer, A., Burnol, A., Cuesta-Marbán, Á., Widmann, C., & Browaeys‐Poly, E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.644633 · Cited by 4
Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes
Antonyan, L., Zhang, X., Ni, A., Peng, H., Alsuwaidi, S., Fleming, P., Zhang, Y., Semenak, A., Macintosh, J., Wu, H., et al. (2025) · Human Molecular Genetics · doi:10.1093/hmg/ddaf003 · Cited by 3
Ser/Thr Phosphatases: The New Frontier for Myeloid Leukemia Therapy?
Amanda, M., Kathryn, G., & Nicole, M. (2011) · InTech eBooks · doi:10.5772/26425 · Cited by 3
Bang, S., Song, J. K., & Lee, K. H. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.11.005 · Cited by 2
Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression
Yang, X., Wen, Y., Ma, X., Qin, S.-Y., Liu, Y., Chen, J., Zhang, H., Goding, C. R., Cui, R., & Liu, T. (2026) · Nature Communications · doi:10.1038/s41467-026-68493-2 · Cited by 2
Chen, G., Yang, C., Liang, M., Yin, J., Gao, B., Nazir, K. A., Wang, J., Xiao, J., Shang, Q., Qian, H., et al. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136561 · Cited by 2
Self-citationSergienko, N. M., Trewin, A. J., Kiriazis, H., Raaijmakers, A. J. A., Donner, D. G., Garside, V. C., Smith, K., Bell, J. R., Mellor, K. M., Delbridge, L. M. D., et al. (2024) · npj Metabolic Health and Disease · doi:10.1038/s44324-024-00033-2 · Cited by 2
Wei, Z., Zhang, S., Bai, K., Liu, Y., Luan, Y., Hu, Z., Li, Y., Qu, Z., Hu, X., Ding, X., et al. (2025) · Development · doi:10.1242/dev.204532 · Cited by 2
RNAi screen to identify protein phosphatases that regulate the NF-kappaB signaling
Wang, G., Li, S., Wang, F., Huang, S., Li, X., Xiong, W., & Zhang, B. (2010) · Frontiers in Biology · doi:10.1007/s11515-010-0050-5 · Cited by 2
Effect of Loading Method on a Peptide Substrate Reporter in Intact Cells
Chadha, R. S., Kalminskii, G., Tierney, A. J., Knopf, J. D., de la Vega, L. L., McElrath, B., & Kovarik, M. L. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b02111 · Cited by 2
A Recombinant Affinity Reagent Specific for a Phosphoepitope of Akt1
McGinnis, J. E., Venegas, L. A., Lopez, H., & Kay, B. K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113305 · Cited by 2
Liu, J., Liu, J., Wang, D., Luo, Q., & Liu, Z. (2021) · Chinese Journal of Analytical Chemistry · doi:10.1016/j.cjac.2021.10.007 · Cited by 2
Whole transcriptome analysis of long noncoding RNA in beryllium sulfate-treated 16HBE cells
Chen, S., Sun, Z., Deng, W., Li, G., Liu, X., & Zhang, Z. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116097 · Cited by 2
Ikeda, S., Sato, K., & Ohama, T. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.149148 · Cited by 2
LAVANYA, V. A., Jamal, S., & Ahmed, N. (2021) · Glycoconjugate Journal · doi:10.1007/s10719-021-09998-4 · Cited by 1
Chen, G., Chen, X., Han, W., Gao, B., Liang, M., Li, T., & Liu, X. (2025) · Neuroscience Letters · doi:10.1016/j.neulet.2025.138181 · Cited by 1
Amino acid–dependent TSC2 dephosphorylation by lysosome–PP2A regulates mTORC1 signaling transduction
Nakamura, T., Nada, S., Matsumoto, M., Othman, N. L., Kosako, H., Ikeda, K., Koshikawa, N., Masumoto, J., Sawasaki, T., Takekawa, M., et al. (2025) · Life Science Alliance · doi:10.26508/lsa.202503206 · Cited by 1
PHLPP is neither a Phosphatase nor a Tumor Suppressor
Leonard, T. A. (2026) · BioEssays · doi:10.1002/bies.70165 · Cited by 1
TogoPhosTAC as a delivery-ready platform for targeted protein dephosphorylation
Chen, Y.-Y., Ke, D.-T., Lee, Y., Chen, H., Lin, H.-Y., Yeh, C.-L., Ko, Y.-C., Tu, M., Yu, C., Hu, Z., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76725-8 · Cited by 1
Variar, G., Pant, T., Singh, A., Ravichandran, A., Swami, S., Kalyanaraman, B., & Dhanasekaran, A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174546 · Cited by 1
Worming to Complete the Insulin/IGF-1 Signaling Cascade: A Dissertation
Padmanabhan, S. (2009) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/40am-yf26
Regulation of protein phosphatase 2A by proteasomal degradation
Oberg, E. A. (2012) · doi:10.17077/etd.i2uanvgl
The Co-chaperones FKBP51 and PP5 Control Nuclear Receptor Phosphorylation and Adipogenesis
Stechschulte, L. A. (2013) · OhioLink ETD Center (Ohio Library and Information Network)
Lawford‐Smith, H. (2015)
The role of glutamine in the regulation of mTOR signalling in pancreatic β-cells
Alghanim, G. (2017) · Leicester Research Archive (University of Leicester)
Investigating the Role of the Vascular Endothelium in Insulin Delivery
Tokarz, V. L., Gao, Y. K., Sugiyama, M. G., Klip, A., & Lee, W. (2017) · The FASEB Journal · doi:10.1096/fasebj.31.1_supplement.883.12
Self-citationStructural Studies on PP2A and Methods in Protein Production
Magnúsdóttir, A. (2008) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
386 The bioenergetics of marine mammals; insights from laboratory and wild studies.
Rosen, D. A. S. (2018) · Journal of Animal Science · doi:10.1093/jas/sky404.335
Hoopes, L. A. (2018) · Journal of Animal Science · doi:10.1093/jas/sky404.336
The role of forkhead box A2 in skeletal muscle
Phua, W. W. T. (2019) · doi:10.32657/10220/49672
The regulation of tumor suppressor PTEN by microRNAs in breast cancer
Chai, C. (2019) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3-hhnk-mz11
Tadele, D. S., Robertson, J. M., Crispin, R., Herrera, M. C., Chlubnová, M., Piechaczyk, L., Durán, P. A., Singh, S. K., Gedde‐Dahl, T., Fløisand, Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.16.089755
The Endothelial Barrier is not Rate-limiting to Insulin Action in the Myocardium
Sanwal, R. (2020) · TSpace (University of Toronto)
Xiaoyan, F., Mingzhe, L. I., Chen, L., Liang, C., Wenli, L. U., Zhiqiang, P., Dongwei, J., Peike, P., Zhao-qin, F., & Xiaomei, L. (2022) · PubMed Central · doi:10.19852/j.cnki.jtcm.20220817.002
Yangjing Capsule Increases Testosterone Production through SET/PI3K/Akt Pathway in Leydig Cell
Xing, D., Liu, Y., Sun, D., Wang, D., Jin, Y., Cai, B., & Jin, B. (2023) · Andrologia · doi:10.1155/2023/4144490
Xu, H., Cai, Y., Yang, H., Li, S., Chen, P., Wei, Z., Wang, F., Wang, Z., & Zhang, Y. (2024) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2024.107457
Hu, Y., Jin, Y., Wu, X., Yang, Y., Li, Y., Li, H., Xiang, S., Song, X., Jiang, L., Zhang, Y., et al. (2019) · Figshare · doi:10.6084/m9.figshare.10730075
Self-citationZhao, J., Chen, G., Li, J., Liu, S., Jin, Q., Zhang, Z., Qi, F., Zhang, J., & Xu, J. (2021) · Figshare · doi:10.6084/m9.figshare.14037694
Zhao, J., Chen, G., Li, J., Liu, S., Jin, Q., Zhang, Z., Qi, F., Zhang, J., & Xu, J. (2021) · Figshare · doi:10.6084/m9.figshare.14037691
ApoE and Intestinal Mucosal Immunity
de Azevedo, O. G. R., Brito, G. A. D. C., Warren, C. A., & Oriá, R. B. (2025) · Springer eBooks · doi:10.1007/978-3-031-52641-1_17-1
ATP-independent phosphate recycling on AGC kinase activation loops induced by alkali metal ionsPreprint
Kubouchi, K., & Mukai, H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.04.674365
ATP-independent phosphate recycling on AGC kinase activation loops induced by alkali metal ionsPreprint
Kubouchi, K., & Mukai, H. (2025) · eLife · doi:10.7554/elife.109457
Narasimhan, S. D. (2010) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/fhpk-6423
Hsiao, K.-C., Ruan, S.-Y., Chen, S.-M., Lai, T.-Y., Chan, R.-H., Zhang, Y.-M., Chu, C.-A., Cheng, H.-C., Tsai, H.-W., Tu, Y.-F., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23658369
Self-citationHu, Y., Jin, Y.-P., Wu, X.-S., Yang, Y., Li, Y.-S., Li, H.-F., Xiang, S.-S., Song, X., Jiang, L., Zhang, Y.-J., et al. (2019) · Figshare · doi:10.6084/m9.figshare.10730087
Self-citationHsiao, K.-C., Ruan, S.-Y., Chen, S.-M., Lai, T.-Y., Chan, R.-H., Zhang, Y.-M., Chu, C.-A., Cheng, H.-C., Tsai, H.-W., Tu, Y.-F., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23658372
Self-citationHu, Y., Jin, Y.-P., Wu, X.-S., Yang, Y., Li, Y.-S., Li, H.-F., Xiang, S.-S., Song, X.-L., Jiang, L., Zhang, Y.-J., et al. (2019) · Figshare · doi:10.6084/m9.figshare.10730078
Self-citationATP-independent phosphate recycling on AGC kinase activation loops induced by alkali metal ionsPreprint
Kubouchi, K., & Mukai, H. (2025) · eLife · doi:10.7554/elife.109457.1
MKRN1 Regulates RANKL‐Induced Differentiation Via Akt and AMPK Pathways
Kim, I., Kim, J. H., Kim, K., Seong, S., Koh, J., & Kim, N. (2025) · Journal of Cellular Physiology · doi:10.1002/jcp.70129
Caractérisation et modélisation des pathologies lymphoïdes présentant des gains du chromosome 21
Laurent, A. P. (2019) · theses.fr (ABES) · doi:10.70675/ed87382fza9bcz45fdz8589zd8c7fb99d3a9
Cell penetrating and interfering peptides as new cancer therapy
Zhang, X. (2017) · theses.fr (ABES) · doi:10.70675/b2053021ze747z4f1azacb7z8a87a14ec9e3
Cristini, A. (2015) · theses.fr (ABES) · doi:10.70675/89719cadza51cz4509zbd9fz3da99c280491
Xu, Y., Liang, W., Tang, Z., Lu, F., Xia, L., Xie, H., Zhong, M., & Li, S. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116773
G0 or no-G0: phosphatase control of quiescence and cell cycle entry
Robinson, E. A., & Barr, A. R. (2026) · Biochemical Society Transactions · doi:10.1042/bst20250091 · Cited by 1
Du, Y., Singh, M., Patil, M. M., Villegas, I. J., Portillo, A., Shang, K., Ben‐Shalom, R., Halmai, J. A. N. M., & Fink, K. D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.26.728012
Targeted dephosphorylation of Tau at the endogenous level promotes its association with microtubulesPreprint
Sathe, G. J., Berterame, F., Cartwright, T. N., Spallek, R., Zhao, J., Bagale, A. R., Gourlay, R., Wood, N. T., Macartney, T., & Sapkota, G. P. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.07.749800
Netrin-1 and UNC5H receptors: role in cell fate determination and carcinogenesis
Bhat, S. A., Nabi, N., & Andrabi, S. (2026) · Biochemical Journal · doi:10.1042/bcj20260374
PP2A targeting: balancing anticancer potential and neurological risk
Chigriai, M., Kraskovskaya, N., Bolshakova, A., Porozova, N. O., Porozov, Y. B., & Pešić, M. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1945801
Cai, X., Xu, X., Zhang, M., & Li, Z. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112965
BindingDB Entry 50046557: Reengineered tricyclic anti-cancer agents.
BindingDB (2016) · UC San Diego · doi:10.7270/q22j6dnh
Metadata
- Authors
- Kuo, Y.-C., Huang, K.-Y., Yang, C.-H., Yang, Y.-S., Lee, W.-Y., & Chiang, C.-W.
- Affiliations
- National Cheng Kung University (TW)
- Corresponding author
- Chiang, Chi-Wu
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 283
- Issue
- 4
- Pages
- 1882-1892
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2045852899
- Cited by
- 367
- References
- 72
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 14 · 2023: 15 · 2022: 23 · 2021: 22 · 2020: 27 · 2019: 20 · 2018: 25 · 2017: 30 · 2016: 20 · 2015: 32 · 2014: 26 · 2013: 18 · 2012: 17
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- Akt, protein phosphatase 2A, PP2A holoenzyme, Akt dephosphorylation, FOXO3, cell proliferation, cell survival, NIH3T3 cells
- MeSH terms
- Animals, Cell Survival, Humans, Interleukin-3, Phosphorylation, Holoenzymes, Gene Silencing, NIH 3T3 Cells, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Protein Phosphatase 2
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
