Human platelet protein ubiquitylation and changes following GPVI activation

Unsworth, A. J., Bombik, I., Pinto-Fernandez, A., McGouran, J. F., Konietzny, R., Zahedi, R. P., Watson, S. P., Kessler, B. M. and Pears, C. J. (2019) Human platelet protein ubiquitylation and changes following GPVI activation. Thrombosis and Haemostasis, 119 (1). pp. 104-116. ISSN 0340-6245 doi: 10.1055/s-0038-1676344

Abstract/Summary

Platelet activators stimulate post-translational modification of signalling proteins to change their activity or their molecular interactions leading to signal propagation. One covalent modification is attachment of the small protein ubiquitin to lysine residues in target proteins. Modification by ubiquitin can either target proteins for degradation by the proteasome or act as a scaffold for other proteins. Pharmacological inhibition of deubiquitylases or the proteasome inhibits platelet activation by collagen, demonstrating a role for ubiquitylation, but relatively few substrates for ubiquitin have been identified and the molecular basis of inhibition is not established. Here we report the ubiquitome of human platelets and changes in ubiquitylated proteins following stimulation by collagen related peptide (CRP-XL). Using platelets from six individuals over three independent experiments, we identified 1634 ubiquitylated peptides derived from 691 proteins, revealing extensive ubiquitylation in resting platelets. 925 of these peptides show an increase of more than 2-fold following stimulation with CRP-XL. Multiple sites of ubiquitylation were 16 identified on a number of proteins including Syk, filamin and integrin heterodimer subunits. This work reveals extensive protein ubiquitylation during activation of human platelets and opens the possibility of novel therapeutic interventions targeting the ubiquitin machinery.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/79825
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Thieme
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