ArticleThe Journal of biological chemistry2012
p38γ Mitogen-activated protein kinase signals through phosphorylating its phosphatase PTPH1 in regulating ras protein oncogenesis and stress response.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.American journal of cancer research · 2024Article
- Review
- Interactions of the protein tyrosine phosphatase PTPN3 with viral and cellular partners through its PDZ domain: insights into structural determinants and phosphatase activity.Frontiers in molecular biosciences · 2023Article
- The Regulatory Mechanism of miR-574-5p Expression in Cancer.Biomolecules · 2022Review
- Pan-cancer analysis supports MAPK12 as a potential prognostic and immunotherapeutic target in multiple tumor types, including in THCA.Oncology letters · 2022Article
- Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.Journal of microbiology (Seoul, Korea) · 2022Article
- The Role of p38γ in Cancer: From review to outlook.International journal of biological sciences · 2021Review
- p38γ MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis.Cancer research · 2020Article
- Article
- Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.Acta pharmaceutica Sinica. B · 2018Review
- NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest.Oncogenesis · 2018Article
- The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulatingThe Journal of biological chemistry · 2017Article
- Article
- Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy.American journal of cancer research · 2016Review
- p38MAPK and Chemotherapy: We Always Need to Hear Both Sides of the Story.Frontiers in cell and developmental biology · 2016Review
- p38γ MAPK Is a Therapeutic Target for Triple-Negative Breast Cancer by Stimulation of Cancer Stem-Like Cell Expansion.Stem cells (Dayton, Ohio) · 2015Article
- Article
- Identification of a ternary protein-complex as a therapeutic target for K-Ras-dependent colon cancer.Oncotarget · 2014Article
- A general assay for monitoring the activities of protein tyrosine phosphatases in living eukaryotic cells.Analytical biochemistry · 2013Article
- p38γ overexpression in gliomas and its role in proliferation and apoptosis.Scientific reports · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatase plays a crucial role in determining cellular fate by inactivating its substrate kinase, but it is not known whether a kinase can vice versa phosphorylate its phosphatase to execute this function. Protein-tyrosine phosphatase H1 (PTPH1) is a specific phosphatase of p38γ mitogen-activated protein kinase (MAPK) through PDZ binding, and here, we show that p38γ is also a PTPH1 kinase through which it executes its oncogenic activity and regulates stress response. PTPH1 was identified as a substrate of p38γ by unbiased proteomic analysis, and its resultant phosphorylation at Ser-459 occurs in vitro and in vivo through their complex formation. Genetic and pharmacological analyses showed further that Ser-459 phosphorylation is directly regulated by Ras signaling and is important for Ras, p38γ, and PTPH1 oncogenic activity. Moreover, experiments with physiological stimuli revealed a novel stress pathway from p38γ to PTPH1/Ser-459 phosphorylation in regulating cell growth and cell death by a mechanism dependent on cellular environments but independent of canonical MAPK activities. These results thus reveal a new mechanism by which a MAPK regulates Ras oncogenesis and stress response through directly phosphorylating its phosphatase.
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Registered trials
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.