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SUMMARY:Dissecting Receptor Tyrosine Kinase Signaling Networks by Quantita
 tive Phosphoproteomics  - Prof. Jesper V. Olsen\, Novo Nordisk Foundation 
 Center for Protein Research (CPR)\, Faculty of Health and Medical Sciences
 \, University of Copenhagen\, Denmark
DTSTART:20180116T130000Z
DTEND:20180116T140000Z
UID:TALK99022@talks.cam.ac.uk
CONTACT:46487
DESCRIPTION:Mass spectrometry (MS)-based quantitative phosphoproteomics is
  a powerful technology for global analysis of cellular signaling networks.
  In particular\, understanding the dynamics of tyrosine phosphorylation (p
 Tyr) is of great importance in eukaryotic cells due to its crucial role in
  regulating intracellular signaling networks controlling cell fate decisio
 ns such as proliferation\, migration\, differentiation\, cell cycle progre
 ssion and apoptosis. I will present how we optimized and employed quantita
 tive phosphoproteomics technologies to delineate receptor tyrosine kinase 
 (RTK) signaling dynamics activated by different growth factor ligands lead
 ing to differential cellular outcome. Reproducible workflows based on phos
 phopeptide enrichment using TiO2 or pTyr-specific antibodies in combinatio
 n with label-free quantitation and LC-MS/MS analysis on Q-Exactive Orbitra
 p type mass spectrometers allowed us to quantify thousands of phosphorylat
 ion sites and derive their kinetic profiles as a function of ligand and st
 imulation time. Using this strategy\, we revealed RTK-specific phospho-reg
 ulation of key adaptor and signaling molecules\, which fine-tune cell migr
 ation and proliferation. Based on a multidisciplinary approach\, which com
 bines quantitative phosphoproteomics and functional cell-based assays\, we
  identified ligand-dependent mechanisms for the control of RTK signaling a
 nd for the specification of long-term cellular outcomes. Our findings unde
 rscore the importance of investigating receptor tyrosine kinase signaling 
 networks in a ligand-dependent manner to identify the key regulatory phosp
 hotyrosine sites\, which can determine cell fate decisions.
LOCATION:CRUK CI Lecture Theatre (Room 001)
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