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Receptor Tyrosine Kinase Ubiquitination and De-Ubiquitination in Signal Transduction and Receptor Trafficking

Critchley, W R; Pellet-Many, C; Ringham-Terry, B; Harrison, M A; Zachary, I C; Ponnamblalam, S


W R Critchley

C Pellet-Many

B Ringham-Terry

M A Harrison

I C Zachary

S Ponnamblalam


Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes. The ubiquitin ligase superfamily comprising the E1, E2 and E3 enzymes are increasingly implicated in this post-translational modification by adding mono- and polyubiquitin tags to RTKs. Conversely, removal of these ubiquitin tags by proteases called de-ubiquitinases (DUBs) enables RTK recycling for another round of ligand sensing and signal transduction. The endocytosis of basal and activated RTKs from the plasma membrane is closely linked to controlled proteolysis after trafficking and delivery to late endosomes and lysosomes. Proteolytic RTK fragments can also have the capacity to move to compartments such as the nucleus and regulate gene expression. Such mechanistic diversity now provides new opportunities for modulating RTK-regulated cellular responses in health and disease states.


Critchley, W. R., Pellet-Many, C., Ringham-Terry, B., Harrison, M. A., Zachary, I. C., & Ponnamblalam, S. (2018). Receptor Tyrosine Kinase Ubiquitination and De-Ubiquitination in Signal Transduction and Receptor Trafficking. Cells, 7(3),

Journal Article Type Article
Acceptance Date Mar 13, 2018
Publication Date Mar 15, 2018
Deposit Date Jun 13, 2019
Publicly Available Date Jun 17, 2019
Journal Cells
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 7
Issue 3
Public URL


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