English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk.

MPS-Authors
/persons/resource/persons85543

Lenz,  C.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons15947

Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

2354959.pdf
(Publisher version), 10MB

Supplementary Material (public)

2354959_Suppl.pdf
(Supplementary material), 12MB

Citation

Justa-Schuch, D., Silvia-Garcia, M., Pilla, E., Engelke, M., Kilisch, M., Lenz, C., et al. (2016). DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk. eLife, 5: e16370. doi:10.7554/eLife.16370.001.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-AE9A-D
Abstract
The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1 strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule pathway.