Informal talk by guest lecturer

02/01/2018 - 11:00 - 12:00
מרצה: 
Tomer Yaron, PhD student
מיקום: 
Faculty seminar room, 2nd floor, Building 212
Affiliation: 
Weill Cornell Medical College & Memorial Sloan Kettering Cancer Center
Abstract: 

The title of the talk: Peptide Library - A New Technology for Predicting Kinase-Protein Phosphorylation Events, and its Application for Cancer and Immunotherapy.

Advisors: Prof.Lewis Cantley, Prof. Olivier Elemento, Weill Cornell Medical College, New York, USA.

Organizer: Coral Haddad (MSc Student, Sarid Lab, coral.haddad@mail.huji.ac.il)

Abstract: Cellular communication and signal transduction are basic mechanisms of multicellular life. The vast majority of signal transduction pathways depend on kinases, enzymes designed to selectively phosphorylate other proteins. Unwelcome changes in the phosphorylation states of proteins can lead to numerous disease, including cancer. Today, phosphoproteomics methods have identified hundreds of thousands of site-specific-phosphorylations in cells and tissues, in numerous different contexts.  There are approximately 500 serine/threonine and tyrosine kinases and assigning a phosphorylation event to a specific kinase is a very important and challenging task. We have found that kinases are highly selective of the amino acid sequence surrounding its Serine (S) / Threonine (T) / Tyrosine (Y) target, termed their 'motif.' Our laboratory has developed a precision technique that measures the core substrate specificities of individual protein kinases with high reproducibility [1]. This essay focuses on the 4-5 amino acids neighboring the S/T/Y of interest, region kinases are exquisitely selective of.  An optimized 10-amino acid substrate motif is generated for each kinase tested. This can be applied to finding novel cellular substrates and conversely can help in linking an uncharacterized phosphorylation events to kinases. Recently, our laboratory has finished characterizing more than 190 Serine/Threonine kinases and 80 Tyrosine kinases, which we used together with computational techniques and machine-learning algorithms, for creating a prediction system for protein-phosphorylation events. In addition, we identified intrinsic properties of the substrate specificities of the entire kinome. This technology reveals interesting hidden patterns underlying the kinome’s substrate specificity, and can be applied for identifying the kinases directly involved in specific pathways, in wide variant of areas, such as diseases mutations, immunotherapy and biosensors.

 [1] Hutti, J.E., Jarrell, E.T., Chang, J.D., Abbott, D.W., Storz, P., Toker, A., Cantley, L.C. and Turk,    B.E., A rapid method for determining protein kinase phosphorylation specificity. Nature methods (2004)