University of Dundee

‘Expanding the catalytic versatility of the protein kinase superfamily’

Event Date: 
Thursday, June 27, 2019 - 13:00 to 14:00
Event Location: 
MSI Small Lecture Theatre
Host: 
Dr Gopal Sapkota
Dr Greg Findlay
Event Speaker: 
Dr Vincent Tagliabracci
Institution: 
UT Southwestern Medical Centre, Dallas, USA
Event Type: 
Seminar
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Vinnie Tagliabracci has established himself as one of the most exciting researchers currently working in the field of protein kinase signalling.

The Tagliabracci laboratory studies unconventional members of the human protein kinase superfamily, including atypical protein kinases and catalytically-inactive “pseudokinases”. As a postdoc in Jack Dixon’s lab, Vinnie discovered a novel family of secreted kinases that was so different from canonical kinases that it was not included on the human kinome tree. He showed that one member, Fam20C, is the bona fide Golgi casein kinase, an enzyme that escaped identification for many years. Fam20C contains a signal peptide that directs it to the lumen of the secretory pathway where it phosphorylates proteins destined for secretion on S-x-E/pS motifs. About 75% of human serum, plasma, and cerebrospinal fluid phosphoproteins are phosphorylated within this motif. Indeed, Fam20C phosphorylates hundreds of secreted proteins and is responsible for generating the majority of the secreted phosphoproteome. Functional annotations of Fam20C substrates suggest roles in a broad spectrum of physiological processes, including lipid metabolism, wound healing, cell migration, biomineralization, inflammation and nervous system development.

 

More recently, the Tagliabracci lab uncovered a previously unrecognized activity for the highly conserved pseudokinase selenoprotein-O (SelO). Approximately 10% of the human protein kinases are classified as pseudokinases because they lack the catalytic residues required for protein phosphorylation. Remarkably, SelO instead transfers AMP from ATP to serine, threonine and tyrosine residues on protein substrates, a modification known as protein “AMPylation”. The crystal structure of SelO reveals a protein kinase-like fold with ATP flipped in the active site, providing a structural basis for AMPylation. SelO pseudokinases localize to the mitochondria and AMPylate proteins involved in redox homeostasis, thereby regulating the cellular response to oxidative stress. However, AMPylation may be a more widespread post-translational modification than previously appreciated, and pseudokinases should be analyzed for alternative transferase activities.

 

Understanding the functional implications of these novel activities of protein kinases and how these modifications impact human biology are major objectives of the Tagliabracci lab.

 

This seminar will be of great interest to any researcher interested in cell signaling and novel activities and functions of the protein kinase superfamily in biology.

For more information on Vinnie Tagliabracci's publications click here:

 

https://scholar.google.com/citations?user=P91T0JQAAAAJ&hl=en

 

Biography:

Vinnie Tagliabracci is an Assistant Professor in the Department of Molecular Biology at UT Southwestern Medical Center. He received his B.S. in Chemistry and Biology from the University of Indianapolis and his Ph.D. in Biochemistry and Molecular Biology from Indiana University under the supervision of Dr. Peter Roach, where he made several important contributions to understanding how elevated levels of glycogen phosphate cause Lafora Disease, a deadly form of epilepsy. In 2010, Vinnie joined the laboratory of Dr. Jack Dixon as a postdoctoral fellow at the University of California, San Diego in La Jolla, CA. There, he discovered a novel family of “secreted” kinases that phosphorylate proteins destined for secretion from the cell. As part of this work, he identified Fam20C as the bona fide "Golgi casein kinase", an enzyme that escaped identification for many years. In 2015, he joined the faculty at UT Southwestern as an Assistant Professor in the Department of Molecular Biology. Vinnie is the recipient of the Esther L. Kinsley dissertation award from Indiana University School of Medicine, a K99/R00 Pathway to Independence award from the National Institutes of Health, a Cancer Prevention Research Institute of Texas (CPRIT) recruitment of first-time, tenure-track faculty member award and is an Endowed Scholar in biomedical research.