Tyrosine phosphorylation directs TACE into extracellular vesicles via unconventional secretion

Show full item record



Permalink

http://hdl.handle.net/10138/308652

Citation

Zhao , Z , Kesti , T , Uğurlu , H , Baur , A S , Fagerlund , R & Saksela , K 2019 , ' Tyrosine phosphorylation directs TACE into extracellular vesicles via unconventional secretion ' , Traffic , vol. 20 , no. 3 , pp. 202-212 . https://doi.org/10.1111/tra.12630

Title: Tyrosine phosphorylation directs TACE into extracellular vesicles via unconventional secretion
Author: Zhao, Zhe; Kesti, Tapio; Uğurlu, Hasan; Baur, Andreas S.; Fagerlund, Riku; Saksela, Kalle
Contributor: University of Helsinki, Medicum
University of Helsinki, Department of Virology
University of Helsinki, Department of Virology
University of Helsinki, Department of Virology
University of Helsinki, Kalle Saksela / Principal Investigator
Date: 2019-03
Language: eng
Number of pages: 11
Belongs to series: Traffic
ISSN: 1398-9219
URI: http://hdl.handle.net/10138/308652
Abstract: When studying how HIV-1 Nef can promote packaging of the proinflammatory transmembrane protease TACE (tumor necrosis factor-alpha converting enzyme) into extracellular vesicles (EVs) we have revealed a novel tyrosine kinase-regulated unconventional protein secretion (UPS) pathway for TACE. When TACE was expressed without its trafficking cofactor iRhom allosteric Hck activation by Nef triggered translocation of TACE into EVs. This process was insensitive to blocking of classical secretion by inhibiting endoplasmic reticulum (ER) to Golgi transport, and involved a distinct form of TACE devoid of normal glycosylation and incompletely processed for prodomain removal. Like most other examples of UPS this process was Golgi reassembly stacking protein (GRASP)-dependent but was not associated with ER stress. These data indicate that Hck-activated UPS provides an alternative pathway for TACE secretion that can bypass iRhom-dependent ER to Golgi transfer, and suggest that tyrosine phosphorylation might have a more general role in regulating UPS.
Subject: 3111 Biomedicine
1182 Biochemistry, cell and molecular biology
ADAM17
exosome
GRASP
Hck
TACE
ACTIVATION
INTRACELLULAR MATURATION
KINASE HCK
TRAFFICKING
MECHANISMS
PLASMA-MEMBRANE
REGULATES GOLGI
TRANSPORT
HIV-NEF
PROTEIN SECRETION
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Zhao_et_al_2018_Traffic.pdf 1.294Mb PDF View/Open
Tyrosine_phosphorylation.pdf 11.16Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record