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GRK2 mediates TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that drives PI3K{gamma}/PREX1 signaling and T cell cytokine secretion Signal Transduction
The immune system includes abundant examples of biologically-relevant cross-regulation of signaling pathways by the T cell antigen receptor (TCR) and the G protein–coupled chemokine receptor, CXCR4. TCR ligation induces transactivation of CXCR4 and TCR–CXCR4 complex formation, permitting the TCR to signal via CXCR4 to activate a phosphatidylinositol 3,4,5-trisphosphate–dependent Rac exchanger 1 protein (PREX1)–dependent signaling pathway that drives robust cytokine secretion by T cells. To understand this receptor heterodimer and its regulation, we characterized the molecular mechanisms required for TCR-mediated TC...
Source: Journal of Biological Chemistry - September 7, 2018 Category: Chemistry Authors: Brittney A. Dinkel, Kimberly N. Kremer, Meagan R. Rollins, Michael J. Medlyn, Karen E. Hedin Tags: Immunology Source Type: research

Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity Metabolism
In conclusion, the relatively low endogenous Spl expression level in insulin-secreting cells contributes to their extraordinary vulnerability to proinflammatory cytokine toxicity and may therefore represent a promising target for β-cell protection in type 1 diabetes mellitus.
Source: Journal of Biological Chemistry - December 8, 2017 Category: Chemistry Authors: Claudine Hahn, Karolina Tyka, Julie D. Saba, Sigurd Lenzen, Ewa Gurgul-Convey Tags: Molecular Bases of Disease Source Type: research

Molecules, Vol. 23, Pages 2828: 8e Protects against Acute Cerebral Ischemia by Inhibition of PI3K γ-Mediated Superoxide Generation in Microglia
Molecules, Vol. 23, Pages 2828: 8e Protects against Acute Cerebral Ischemia by Inhibition of PI3Kγ-Mediated Superoxide Generation in Microglia Molecules doi: 10.3390/molecules23112828 Authors: Linna Wang Xiaoli Wang Tingting Li Yihua Zhang Hui Ji The inflammatory response mediated by microglia plays a critical role in the progression of ischemic stroke. Phosphoinositide 3-kinase gamma (PI3Kγ) has been implicated in multiple inflammatory and autoimmune diseases, making it a promising target for therapeutic intervention. The aim of this study was to evaluate the efficacy of 8e, a hydrogen sulfi...
Source: Molecules - October 31, 2018 Category: Chemistry Authors: Linna Wang Xiaoli Wang Tingting Li Yihua Zhang Hui Ji Tags: Article Source Type: research

{beta}-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling Signal Transduction
In this study, we discovered a novel protein interaction between the glucocorticoid receptor and β-arrestin-1, a scaffold protein with a well-established role in G protein–coupled receptor signaling. Using co-immunoprecipitation and in situ proximity ligation assays in A549 cells, we observed that β-arrestin-1 and unliganded GR interact in the cytoplasm and that, following glucocorticoid binding, the protein complex is found in the nucleus. We show that siRNA-mediated β-arrestin-1 knockdown alters GR protein turnover by up-regulating the E3 ubiquitin ligase Pellino-1, which catalyzes GR ubiquitination and thereby mark...
Source: Journal of Biological Chemistry - July 18, 2019 Category: Chemistry Authors: Maria G. Petrillo, Robert H. Oakley, John A. Cidlowski Tags: Signal Transduction Source Type: research