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PXD054405

PXD054405 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMicrocystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells
DescriptionMicrocystin-LR (MCLR) exposure has been associated with development of hepatocellular carcinoma (HCC). Many of the carcinogenic mechanisms for MCLR have been attributed to the induction of cell survival and proliferation through altered protein phosphorylation pathways by inhibition of protein phosphatases 1 (PP1) and PP2A. The current study determined MCLR effects on the phosphoproteome in human HepaRG cells. Differentiated HepaRG cells were treated with either vehicle or MCLR followed by phosphoproteomic analysis and Western blotting of MAPK-activated proteins. MCLR decreased cell viability at 24 h at doses as low as 0.03 µM. MCLR also caused a dose-dependent increase in phosphorylation of signaling and stress kinases. The number of decreased phosphosites by 0.1 µM MCLR was similar between the 2 h (212) and 24 h (154) timepoints. In contrast, a greater number of phosphosites were increased at 24 h (567) versus the 2 h timepoint (136), indicating the hyperphosphorylation state caused by MCLR-mediated inhibition of PPs is time-dependent. A kinase perturbation analysis predicted that MCLR exposure at both 2 h and 24 h increased the function of aurora kinase B (AURKB), checkpoint kinase 1 (CHEK1), and serum and glucocorticoid-regulated kinase 1 (SGK1). STRING database analysis of the phosphosites altered by MCLR exposure revealed pathways associated with cell proliferation and survival, including ribosomal protein S6 kinase (RSK), and vascular endothelial growth factor receptor (VEGFR2)-mediated vascular permeability. In addition, several cancer-related KEGG pathways were enriched at both 2 h and 24 h timepoints, and multiple cancer-related disease-gene associations were identified at the 24 h timepoint. Many of the kinases and pathways described above play crucial roles in the development of HCC by affecting processes such as invasion and metastasis. Overall, our data indicate that MCLR-mediated changes in protein phosphorylation involve biological pathways related to carcinogenesis that may contribute to the development of HCC.
HostingRepositoryPRIDE
AnnounceDate2025-02-05
AnnouncementXMLSubmission_2025-02-05_12:27:08.193.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBhagwat Prasad
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-30 10:40:14ID requested
12025-02-05 12:27:09announced
Publication List
Ikumawoyi VO, Lynch KD, Iverson DT, Call MR, Yue GE, Prasad B, Clarke JD, Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells. Toxicon, 249():108072(2024) [pubmed]
10.1016/j.toxicon.2024.108072;
Keyword List
submitter keyword: protein phosphatase, mitogen-activated protein kinase, microcystin-LR, protein phosphorylation, phosphoproteomics,HepaRG cells
Contact List
Bhagwat Prasad
contact affiliationProfessor, Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, United States
contact emailbhagwat.prasad@wsu.edu
lab head
Bhagwat Prasad
contact affiliationWashington State University
contact emailbhagwat.prasad@wsu.edu
dataset submitter
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