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Colitis is associated with loss of LHPP and up-regulation of histidine phosphorylation in intestinal epithelial cells

View ORCID ProfileMarkus Linder, Dritan Liko, Venkatesh Kancherla, View ORCID ProfileSalvatore Piscuoglio, View ORCID ProfileMichael N. Hall
doi: https://doi.org/10.1101/2020.10.11.334334
Markus Linder
1Biozentrum, University of Basel, CH-4056 Basel, Switzerland
2Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland
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Dritan Liko
1Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Venkatesh Kancherla
3Institute of Medical Genetics and Pathology, University Hospital Basel, CH-4031 Basel, Switzerland
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Salvatore Piscuoglio
3Institute of Medical Genetics and Pathology, University Hospital Basel, CH-4031 Basel, Switzerland
4Visceral Surgery and Precision Medicine research laboratory, Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland
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Michael N. Hall
1Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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  • For correspondence: m.hall@unibas.ch
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Abstract

Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis (1). Using novel monoclonal antibodies to detect pHis (2), we recently reported that loss of the histidine phosphatase LHPP results in elevated pHis levels in hepatocellular carcinoma (3). Here, we show that intestinal inflammation correlates with loss of LHPP, in 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, ablation of Lhpp did not cause increased pHis or promote intestinal inflammation in physiological conditions or after DSS treatment. Our observations suggest that increased histidine phosphorylation plays a role in colitis, but loss of LHPP is not sufficient to increase pHis or to cause inflammation in the intestine.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 11, 2020.
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Colitis is associated with loss of LHPP and up-regulation of histidine phosphorylation in intestinal epithelial cells
Markus Linder, Dritan Liko, Venkatesh Kancherla, Salvatore Piscuoglio, Michael N. Hall
bioRxiv 2020.10.11.334334; doi: https://doi.org/10.1101/2020.10.11.334334
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Colitis is associated with loss of LHPP and up-regulation of histidine phosphorylation in intestinal epithelial cells
Markus Linder, Dritan Liko, Venkatesh Kancherla, Salvatore Piscuoglio, Michael N. Hall
bioRxiv 2020.10.11.334334; doi: https://doi.org/10.1101/2020.10.11.334334

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