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SUMMARY:How do receptor tyrosine phosphatases signal? - Hayley Sharpe\, Ba
 braham Institute
DTSTART:20230516T113000Z
DTEND:20230516T123000Z
UID:TALK200992@talks.cam.ac.uk
CONTACT:Michael Boemo
DESCRIPTION:Phosphotyrosine regulation is a fundamental process in cells\,
  critical for cell adhesion\, migration\, and growth. However\, its dysreg
 ulation is associated with a variety of diseases. Kinases and phosphatases
 \, or PTPs\, function together allowing for rapid and dynamic adaptation o
 f cells to changing conditions. Traditionally viewed as "off-switches" to 
 signalling\, PTPs can in fact function as both tumour suppressors and onco
 genes. Receptor protein tyrosine phosphatases (RPTPs) are type I transmemb
 rane 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 sup
 pressor protein PTPRK regulates cell adhesion and is stabilised at cell-ce
 ll contacts via extracellular homophilic interactions. Our investigation o
 f PTPRK function in tumour suppression has led to the surprising discovery
  of catalysis-independent inhibition of growth factor and TGFβ signalling
 . We propose that PTPRK functions as a contact sensor\, accumulating with 
 cell density and mediating contact inhibition signalling by increasing bin
 ding sites and sequestration of key proteins. As a TGFβ target gene\, PTP
 RK is an ideal candidate for sensing repair\, supported by impaired respon
 ses 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 i
 mplications for the development of therapeutic strategies targeting PTPs. 
 Our findings also open up new avenues for understanding the interplay betw
 een kinases and phosphatases in phosphotyrosine regulation.
LOCATION:Seminar Room\, Department of Pathology\, Tennis Court Road
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