Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity

Haagenson, Kelly K.; Zhang, Jessica Wei; Xu, Zhengfan; Shekhar, Malathy P.V.; Wu, Gen Sheng

doi:10.18632/oncotarget.1795

Cited by 11 publications

(8 citation statements)

References 28 publications

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“…(iii) As bispecific protein phosphatases, MKP proteins can inactivate the phosphorylated MAPK through dephosphorylation at residues Ser and Tyr of TXY motif. Among them, MKP1 and MKP2 can dephosphorylate ERK, JNK, and p38, which negatively regulated MAPK cascades (55). Phosphorylation at residues Ser359 and Ser364 in MKP1 by ERK1 and ERK2 enhanced MKP1 stability and protected it from proteasome-mediated degradation (56).…”

Section: Mapk Pathways Were Dysregulated In Nfpasmentioning

confidence: 99%

Multiomics-Based Signaling Pathway Network Alterations in Human Non-functional Pituitary Adenomas

Long

Cheng

et al. 2019

Front. Endocrinol.

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Non-functional pituitary adenoma (NFPA) seriously affects hypothanamus-pituitary-target organ axis system, with a series of molecule alterations in the multiple levels of genome, transcriptome, proteome, and post-translational modifications, and those molecules mutually interact in a molecular-network system. Meta analysis coupled with IPA pathway-network program was used to comprehensively analyze nine sets of documented NFPA omics data, including NFPA quantitative transcriptomics data [280 differentially expressed genes (DEGs)], NFPA quantitative proteomics data [50 differentially expressed proteins (DEPs)], NFPA mapping protein data (218 proteins), NFPA mapping protein nitration data (9 nitroproteins and 3 non-nitrated proteins), invasive NFPA quantitative transriptomics data (346 DEGs), invasive NFPA quantitative proteomics data (57 DEPs), control mapping protein data (1469 proteins), control mapping protein nitration data (8 nitroproteins), and control mapping phosphorylation data (28 phosphoproteins). A total of 62 molecular-networks with 861 hub-molecules and 519 canonical-pathways including 54 cancer-related canonical pathways were revealed. A total of 42 hub-molecule panels and 9 canonical-pathway panels were identified to significantly associate with tumorigenesis. Four important molecular-network systems, including PI3K/AKT, mTOR, Wnt, and ERK/MAPK pathway-systems, were confirmed in NFPAs by PTMScan experiments with altered expression-patterns and phosphorylations. Nineteen high-frequency hub-molecules were also validated in NFPAs with PTMScan experiment with at least 2.5-fold changes in expression or phosphorylation, including ERK, ERK1/2, Jnk, MAPK, Mek, p38 MAPK, AKT, PI3K complex, p85, PKC, FAK, Rac, Shc, HSP90, NFκB Complex, histone H3, AP1, calmodulin, and PLC. Furthermore, mTOR and Wnt pathway-systems were confirmed in NFPAs by immunoaffinity Western blot analysis, with significantly decreased expression of PRAS40 and increased phosphorylation levels of p-PRAS40 (Thr246) in mTOR pathway in NFPAs compared to controls, and with the decreased protein expressions of GSK-3β and GSK-3β, significantly increased phosphorylation levels of p-GSK3α (Ser21) and p-GSK3β (Ser9), and increased expression level of β-catenin in Wnt pathway in NFPAs compared to Long et al. Molecular Networks of Non-functional Pituitary Adenomas controls. Those findings provided a comphrensive and large-scale pathway network data for NFPAs, and offer the scientific evidence for insights into the accurate molecular mechanisms of NFPA and discovery of the effective biomarkers for diagnosis, prognosis, and determination of therapeutic targets.

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Section: Mapk Pathways Were Dysregulated In Nfpasmentioning

confidence: 99%

Multiomics-Based Signaling Pathway Network Alterations in Human Non-functional Pituitary Adenomas

Long

Cheng

et al. 2019

Front. Endocrinol.

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“…MKP-1, the first defined member of MKPs [8], has been regarded as an important regulator of innate immune response and tumorigenesis by deactivating both MAP kinases and NFκB pathway in immune cells [9–15]. Previous study has shown that MKP-1 transcripts are detected in E14.5 mouse embryonic reproductive system by RNA in situ hybridization [16].…”

Section: Introductionmentioning

confidence: 99%

MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways

et al. 2016

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Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation. In addition, MKP-1 staining was strongly detected in nuclei and peri-nuclear regions of cytoplasm in the Sertoli cells, and it was presented at Sertoli cell tight junctions (TJs) at stages VII-VIII after LPS treatment. Moreover, we demonstrated that MKP-1 was capable of attenuating LPS-induced decrease of occludin by interaction with p38 MAP kinase and IκBα molecules. Taken together, our data highlight that MKP-1 was an important endogenous suppressor of innate immune responses involved in the regulation of BTB barrier dynamic. This study thus might offer novel targets for treating inflammatory diseases in the testis.

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“…By changing the phosphorylation site of RAF1, appl1 activates the mapk/erk cell-signal pathway 29 . The mapk/erk pathway promotes tumour cell proliferation and suppresses tumour cell apoptosis 30 . The mapk/erk pathway activates many oncogenes-for example, COX2 31 .…”

Section: Discussionmentioning

confidence: 99%

Expression of APPL1 Is Correlated with Clinicopathologic Characteristics and Poor prognosis in Patients with Gastric Cancer

Zhai¹,

Song²,

Zhu³

et al. 2016

Current Oncology

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Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity

Cited by 11 publications

References 28 publications

Multiomics-Based Signaling Pathway Network Alterations in Human Non-functional Pituitary Adenomas

Multiomics-Based Signaling Pathway Network Alterations in Human Non-functional Pituitary Adenomas

MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways

Expression of APPL1 Is Correlated with Clinicopathologic Characteristics and Poor prognosis in Patients with Gastric Cancer

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