Arthur Weiss to Speak at Protein Kinases & Drug Design Conference (October 23-24, 2014 in Boston)
Arthur Weiss, Ephraim P. Engleman Distinguished Professor at University of California San Francisco will give a keynote presentation on, "Controlling T Cell Receptor Signaling with Genetically Selective Kinase Inhibitors" at the 3rd Protein Kinases & Drug Design Conference (October 23-24, 2014 in Boston, MA) by GTCbio.
- (1888PressRelease) July 31, 2014 - T cell antigen receptor (TCR) signal transduction is initiated by the sequential and regulated action of the Lck and ZAP-70 cytoplasmic tyrosine kinases. The importance of ZAP-70 in normal and pathological conditions have identified it as an attractive therapeutic target. By mutating the ZAP-70 gatekeeper residue and using bulky PP1 analogs, we have developed a genetically-selective system for ZAP-70 inhibition. Results from this system support the notion that ZAP-70 catalytic function is critically important in most, but perhaps not all, mature peripheral T cell functions.
Recent studies combining a Nur77-GFP strength of signaling reporter with the ZAP-70 analog sensitive system has allowed us to define a very discrete signaling threshold for T cell activation. The SRC family kinase LCK is also critical for the initiation of TCR signaling function and of ZAP-70 function. In T cells, SRC kinases are regulated, in part, by the opposing actions of the receptor tyrosine phosphatase CD45 and the cytoplasmic tyrosine kinase CSK. We have applied the genetically-selective inhibitor system to probe the importance of CSK function. These studies suggest a very dynamic mechanism is involved in controlling SRC kinase activity in the basal state. Inhibition of CSK function can lead to activation of TCR-dependent signaling. These studies have also revealed a critical negative regulatory function of the actin cytoskeleton that acts downstream of the proximal TCR signaling kinases. Thus, we demonstrate the utility and power of probing TCR signaling function negatively and positively with genetically selective systems using tyrosine kinase inhibitors.
Benefits of talk:
- Gain familiarity with TCR signaling
- Understand the functions of cytoplasmic kinases involved in the initiation of TCR signaling
- Appreciate mechanisms that control basal signaling in T cells
- Appreciate the roles of kinases and phosphatases in controlling Src family kinases
GTCbio's 3rd Protein Kinases & Drug Design Conference, to be held in October 23-24, 2014 in Boston, MA, will bring together speakers representing world-leading academic centers and pharmaceutical companies to discuss how to overcome the many hurdles and answer exciting key questions. Experts will also share their positive and negative experiences on how predictive preclinical models are with clinical efficacy and toxicology.
This conference is part of our Protein Discovery Summit 2014, which consists of this and three additional parallel conferences shown below:
- Protein-Protein Interaction
- Antibody & Protein Therapeutics
- Protein Expression, Purification & Characterization
- Protein Kinases & Drug Design
For more information, please visit www.gtcbio.com
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