Results 131 to 140 of about 293,862 (300)

A Bifunctional T3SS‐Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase

open access: yesAdvanced Science, EarlyView.
Pathogenic bacteria exploit the metalloprotease effector NleD to subvert host defenses. Structural, biochemical, and infection analyses reveal a bifunctional mechanism by which NleD binds and inhibits the host phosphatase PPM1A while preserving its proteolytic activity against MAPKs.
Yaakov Socol   +18 more
wiley   +1 more source

The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H\u3csub\u3e2\u3c/sub\u3e0\u3csub\u3e2\u3c/sub\u3e and plays an integral role in insulin signal transduction [PDF]

open access: yes, 2004
Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade.
Arnold, Rebecca S.   +7 more
core   +1 more source

Targeting UXS1‐Dependent Glucuronate Detoxification Potentiates Metformin's Anti‐Tumor Efficacy in Lung Adenocarcinoma

open access: yesAdvanced Science, EarlyView.
This study reveals that metformin promotes glucuronic acid metabolism in lung adenocarcinoma by activating UGDH S476 phosphorylation and enhancing the conversion of UDPG to UDPGA based on metabolomics analysis. Through compound virtual screening, it is found that plantainoside targeting UGDH downstream UXS1 leads to UDPGA toxicity accumulation ...
Qihai Sui   +14 more
wiley   +1 more source

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

open access: yesAdvanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel   +16 more
wiley   +1 more source

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

open access: yesAdvanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang   +14 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

open access: yesAdvanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong   +5 more
wiley   +1 more source

Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update

open access: yesPharmacological Research
Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one of the most important drug targets in the 21st century.
Robert Roskoski, Jr.
doaj   +1 more source

Time‐Controlled Refrigerated Stem Cell Therapy Mitigates Scleroderma Fibrosis via Modulation of Mitochondrial Autophagy and Gut Metabolism

open access: yesAdvanced Science, EarlyView.
This study established an RT‐MSCs‐based therapeutic approach for scleroderma in mice. RT‐MSCs attenuated fibrosis by regulating mitochondrial autophagy and restored gut microbiota homeostasis. Metabolomic analyses confirmed recovery of key metabolites, and RT‐MSCs demonstrated favorable lesion targeting and safety profiles.
Xue Xia   +5 more
wiley   +1 more source

Experimental approaches to understanding the role of protein phosphorylation in the regulation of neuronal function [PDF]

open access: yes, 1983
Studies by Earl Sutherland and his colleagues on hormonal regulation of the breakdown of glycogen in liver resulted in the discovery that the first step in the action of many hormones is to increase the synthesis of cAMP by activating adenylate cyclase ...
Kennedy, Mary B.
core  

β‐Adrenergic Signaling Promotes Anti‐Tumor Immunity in TP53‐mutant Oral Squamous Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
β‐adrenergic stimulation enhances anti‐tumor immunity in TP53‐deficient oral squamous cell carcinoma by inducing tumor‐derived secretion of CXCL10, which attracts and activates cytotoxic CD8+ T cells. The findings demonstrate that β‐adrenergic signaling alters tumor–immune interactions via CXCL10‐mediated paracrine activation, revealing a neuro‐immune ...
Frederico O. Gleber‐Netto   +20 more
wiley   +1 more source

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