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

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

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Title: DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk
Author: Justa-Schuch, Daniela; Silva-Garcia, Maria; Pilla, Esther; Engelke, Michael; Kilisch, Markus; Lenz, Christof; Möller, Ulrike; Nakamura, Fumihiko; Urlaub, Henning; Geiss-Friedlander, Ruth

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Citation: Justa-Schuch, Daniela, Maria Silva-Garcia, Esther Pilla, Michael Engelke, Markus Kilisch, Christof Lenz, Ulrike Möller, Fumihiko Nakamura, Henning Urlaub, and Ruth Geiss-Friedlander. 2016. “DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk.” eLife 5 (1): e16370. doi:10.7554/eLife.16370. http://dx.doi.org/10.7554/eLife.16370.
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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. DOI: http://dx.doi.org/10.7554/eLife.16370.001
Published Version: doi:10.7554/eLife.16370
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039030/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407611
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