Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells
Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistid...
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2158 |
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| author | Markus Linder Dritan Liko Venkatesh Kancherla Salvatore Piscuoglio Michael N. Hall |
| author_facet | Markus Linder Dritan Liko Venkatesh Kancherla Salvatore Piscuoglio Michael N. Hall |
| author_sort | Markus Linder |
| collection | DOAJ |
| description | Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) results in elevated pHis levels in hepatocellular carcinoma. Here, we show that intestinal inflammation correlates with the loss of LHPP in dextran sulfate sodium (DSS)-treated mice and in inflammatory bowel disease (IBD) patients. Increased histidine phosphorylation was observed in intestinal epithelial cells (IECs), as determined by pHis immunofluorescence staining of colon samples from a colitis mouse model. However, the ablation of <i>Lhpp</i> did not cause increased pHis or promote intestinal inflammation under physiological conditions or after DSS treatment. Our observations suggest that increased histidine phosphorylation plays a role in colitis, but the loss of LHPP is not sufficient to increase pHis or to cause inflammation in the intestine. |
| first_indexed | 2024-03-11T00:07:05Z |
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| language | English |
| last_indexed | 2024-03-11T00:07:05Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-ffac672ec51d4a939a0fb419e563fff22023-11-19T00:20:14ZengMDPI AGBiomedicines2227-90592023-08-01118215810.3390/biomedicines11082158Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial CellsMarkus Linder0Dritan Liko1Venkatesh Kancherla2Salvatore Piscuoglio3Michael N. Hall4Biozentrum, University of Basel, 4056 Basel, SwitzerlandBiozentrum, University of Basel, 4056 Basel, SwitzerlandInstitute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, SwitzerlandInstitute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, SwitzerlandBiozentrum, University of Basel, 4056 Basel, SwitzerlandProtein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) results in elevated pHis levels in hepatocellular carcinoma. Here, we show that intestinal inflammation correlates with the loss of LHPP in dextran sulfate sodium (DSS)-treated mice and in inflammatory bowel disease (IBD) patients. Increased histidine phosphorylation was observed in intestinal epithelial cells (IECs), as determined by pHis immunofluorescence staining of colon samples from a colitis mouse model. However, the ablation of <i>Lhpp</i> did not cause increased pHis or promote intestinal inflammation under physiological conditions or after DSS treatment. Our observations suggest that increased histidine phosphorylation plays a role in colitis, but the loss of LHPP is not sufficient to increase pHis or to cause inflammation in the intestine.https://www.mdpi.com/2227-9059/11/8/2158histidine phosphorylationLHPPinflammatory bowel diseasecolitis |
| spellingShingle | Markus Linder Dritan Liko Venkatesh Kancherla Salvatore Piscuoglio Michael N. Hall Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells Biomedicines histidine phosphorylation LHPP inflammatory bowel disease colitis |
| title | Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells |
| title_full | Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells |
| title_fullStr | Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells |
| title_full_unstemmed | Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells |
| title_short | Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells |
| title_sort | colitis is associated with loss of the histidine phosphatase lhpp and upregulation of histidine phosphorylation in intestinal epithelial cells |
| topic | histidine phosphorylation LHPP inflammatory bowel disease colitis |
| url | https://www.mdpi.com/2227-9059/11/8/2158 |
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