ARL11 regulates lipopolysaccharide-stimulated macrophage activation by promoting mitogen-activated protein kinase (MAPK) signaling
| Autor: | Gaurav Kumar, Amandeep Kaur, Harmeet Kaur, Amit Tuli, Subhash B. Arya |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Lipopolysaccharides Salmonella typhimurium medicine.medical_treatment p38 mitogen-activated protein kinases Sequence Homology macrophage Biochemistry p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Mice 0302 clinical medicine Salmonella medicine Macrophage Animals Humans Editors' Picks Amino Acid Sequence mitogen-activated protein kinase (MAPK) ARL11 Phosphorylation Protein kinase A Extracellular Signal-Regulated MAP Kinases Molecular Biology GTPase biology extracellular-signal-regulated kinase (ERK) Kinase Chemistry ADP-Ribosylation Factors Macrophages ARLTS1 Cell Biology Macrophage Activation Cell biology Mice Inbred C57BL 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Mitogen-activated protein kinase Salmonella Infections biology.protein Female Signal transduction lipopolysaccharide (LPS) Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | ADP-ribosylation factor-like GTPase 11 (ARL11) is a cancer-predisposing gene that has remained functionally uncharacterized to date. In this study, we report that ARL11 is endogenously expressed in mouse and human macrophages and regulates their activation in response to lipopolysaccharide (LPS) stimulation. Accordingly, depletion of ARL11 impaired both LPS-stimulated pro-inflammatory cytokine production by macrophages and their ability to control intracellular replication of Salmonella. LPS-stimulated activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) was substantially compromised in Arl11-silenced macrophages. In contrast, increased expression of ARL11 led to constitutive ERK1/2 phosphorylation, resulting in macrophage exhaustion. Finally, we found that ARL11 forms a complex with phospho-ERK in macrophages within minutes of LPS stimulation. Taken together, our findings establish ARL11 as a novel regulator of ERK signaling in macrophages, required for macrophage activation and immune function. |
| Databáze: | OpenAIRE |
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