Evidence map›Paper›PMID 35294873›Full record

ArticleCell reports2022

Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake.

Song-Hua Hu, Xia-Di He, Ji Nie, Jun-Li Hou, Jiang Wu, Xiao-Yan Liu, Yun Wei, Hui-Ru Tang, Wen-Xing Sun, Shu-Xian Zhou and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 2 countries.

Song-Hua HuObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Xia-Di HeObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Ji NieObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Jun-Li HouDepartment of Chemistry, Fudan University, Shanghai 200438, P.R. China.
Jiang WuHefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, P. R. China.
Xiao-Yan LiuCAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China.
Yun WeiObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Hui-Ru TangObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China.
Wen-Xing SunObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Shu-Xian ZhouObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Yi-Yuan YuanObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Yan-Peng AnObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China.
Guo-Quan YanObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China.
Yan LinObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China.
Peng-Cheng LinKey Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai University for Nationalities, Xining 810007, P. R. China.
Jean J ZhaoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ming-Liang YeCAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China. Electronic address: mingliang@dicp.ac.cn.
Jian-Yuan ZhaoObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China. Electronic address: zhaojy@fudan.edu.cn.
Wei XuObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China. Electronic address: xuwei_0706@fudan.edu.cn.
Shi-Min ZhaoObstetrics & Gynecology Hospital of Fudan University, Institutes of Metabolism and Integrative Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Shanghai 200438, P.R. China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Medical Epigenetics, and Children's Hospital of Fudan University, Shanghai 200438, P.R. China; Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai University for Nationalities, Xining 810007, P. R. China. Electronic address: zhaosm@fudan.edu.cn.
Fudan University · CNDalian Institute of Chemical Physics · CNBroad Institute · USQinghai University for Nationalities · CNUniversity of Science and Technology of China · CN

Funding

Integrating targeted therapy and immunotherapy to break through cancerR35CA210057 · NCI · DANA-FARBER CANCER INST · PI Jean Zhao · 2016 to 2026
$10.8M
NCI NIH HHS R35 CA210057
6 · The paper itself

Abstract

Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2. DHA-administered mice exhibit altered phosphorylation of proteins in signaling pathways. Methylene bridge-containing DHA/EPA acylate δ1 carbon of tryptophan 448/543 in PDK1 and tryptophan 414 in AKT2 via free radical pathway, recruit both the proteins to the cytoplasmic membrane, and activate PI3K signaling and glucose uptake in a tryptophan acylation-dependent but insulin-independent manner in cultured cells and in mice. DHA/EPA deplete cytosolic PDK1 and AKT2 and induce insulin resistance. Akt2 knockout in mice abrogates DHA/EPA-induced PI3K-AKT signaling. Our results identify PUFA's methylene bridge tryptophan acylation, a protein fatty acylation that regulates cell signaling and may underlie multifaceted effects of methylene-bridge-containing PUFAs.

Indexed as

Phosphatidylinositol 3-KinasesTryptophanAcylationAnimalsDocosahexaenoic AcidsEicosapentaenoic AcidFatty Acids, UnsaturatedGlucoseMiceProto-Oncogene Proteins c-aktSignal TransductionDocosahexaenoic AcidsEicosapentaenoic AcidFatty Acids, UnsaturatedGlucosePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTryptophanAkt signalingDHA/EPAfatty acylation

Identifiers

PMID35294873
PMCPMC9396916
OpenAlexW4220908852

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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.