Protein tyrosine phosphatase κ and SHP-1 are involved in the regulation of cell-cell contacts at adherens junctions in the exocrine pancreas
- J Schnekenburger1,*,
- J Mayerle2,*,
- B Krüger3,
- I Buchwalow1,
- F U Weiss2,
- E Albrecht3,
- V E Samoilova1,
- W Domschke1,
- M M Lerch2
- 1Department of Medicine B, Westfälische Wilhelms-Universität Münster, Münster, Germany
- 2Department of Gastroenterology, Endocrinology, and Nutrition, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany
- 3Department of Pathology, Division of Medical Biology, Universität Rostock, Rostock, Germany
- Correspondence to:
Professor M M Lerch
Department of Gastroenterology, Endocrinology, and Nutrition, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Loeffler-Strasse 23a, 17487 Greifswald, Germany;
- Accepted 12 April 2005
- Revised 15 March 2005
- Published Online First 29 June 2005
Background: We have previously shown that cell contacts between pancreatic acinar cells dissociate early in pancreatitis and that this is a prerequisite for the development of pancreatic oedema. Here we studied the underlying mechanism.
Methods: Employing experimental caerulein induced pancreatitis in vivo and isolated pancreatic acini ex vivo, in conjunction with protein chemistry, morphology, and electron microscopy, we determined whether cell contact regulation in the pancreas requires or involves: (1) changes in cadherin-catenin protein expression, (2) tyrosine phosphorylation of adhesion proteins, or (3) alterations in the actin cytoskeleton.
Results: During initial cell-cell contact dissociation at adherens junctions, expression of adhesion proteins remained stable. At time points of dissociated adherens junctions, the cadherin-catenin complex was found to be tyrosine phosphorylated and internalised. The receptor type protein tyrosine phosphatase (PTP)κ was constitutively associated with the cadherin-catenin complex at intact cell contacts whereas following the dissociation of adherens junctions, the internalised components of the cadherin-catenin complex were tyrosine phosphorylated and associated with the cytosolic PTP SHP-1. In isolated acini, inhibition of endogenous protein tyrosine phosphatases alone was sufficient to induce dissociation of adherens junctions analogous to that found with supramaximal caerulein stimulation. Dissociation of actin microfilaments had no effect on adherens junction integrity.
Conclusions: These data identify tyrosine phosphorylation as the key regulator for cell contacts at adherens junctions and suggest a definitive role for the protein tyrosine phosphatases PTPκ and SHP-1 in the regulation, maintenance, and restitution of cell adhesions in a complex epithelial organ such as the pancreas.
- PTP, protein tyrosine phosphatase
- PTK, protein tyrosine kinase
- DMEM, Dulbecco’s modified Eagle’s medium
- SDS, sodium dodecyl sulphate
- BSA, bovine serum albumin
- EM, electron microscopy
- cadherin-catenin complex
- protein tyrosine phosphatases
- tyrosine phosphorylation
↵* J Schnekenburger and J Mayerle contributed equally to this paper.
Conflict of interest: None declared.
Published online first 29 June 2005