How do receptor tyrosine phosphatases signal?

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• Hayley Sharpe, Babraham Institute
• Tuesday 16 May 2023, 12:30-13:30
• Seminar Room, Department of Pathology, Tennis Court Road.

If you have a question about this talk, please contact Michael Boemo.

Phosphotyrosine regulation is a fundamental process in cells, critical for cell adhesion, migration, and growth. However, its dysregulation is associated with a variety of diseases. Kinases and phosphatases, or PTPs, function together allowing for rapid and dynamic adaptation of cells to changing conditions. Traditionally viewed as “off-switches” to signalling, PTPs can in fact function as both tumour suppressors and oncogenes. Receptor protein tyrosine phosphatases (RPTPs) are type I transmembrane proteins that link extracellular sensing to intracellular catalysis. While their signalling principles remain to be fully understood, they are known to be important in numerous physiological processes. The tumour suppressor protein PTPRK regulates cell adhesion and is stabilised at cell-cell contacts via extracellular homophilic interactions. Our investigation of PTPRK function in tumour suppression has led to the surprising discovery of catalysis-independent inhibition of growth factor and TGF β signalling. We propose that PTPRK functions as a contact sensor, accumulating with cell density and mediating contact inhibition signalling by increasing binding sites and sequestration of key proteins. As a TGF β target gene, PTPRK is an ideal candidate for sensing repair, supported by impaired responses to DSS -induced colitis in PTPRK KO mice. Our model for RPTP signalling goes beyond dephosphorylation and does not require extracellular ligands, providing a novel perspective for PTP signalling. This has significant implications for the development of therapeutic strategies targeting PTPs. Our findings also open up new avenues for understanding the interplay between kinases and phosphatases in phosphotyrosine regulation.

This talk is part of the Cellular and Molecular Pathology Seminars series.

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• Cellular and Molecular Pathology Seminars
• Seminar Room, Department of Pathology, Tennis Court Road

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