LTK is an ER-resident receptor tyrosine kinase that regulates secretion.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
05 08 2019
05 08 2019
Historique:
received:
12
03
2019
revised:
17
04
2019
accepted:
15
05
2019
pubmed:
23
6
2019
medline:
19
5
2020
entrez:
23
6
2019
Statut:
ppublish
Résumé
The endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting, and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.
Identifiants
pubmed: 31227593
pii: jcb.201903068
doi: 10.1083/jcb.201903068
pmc: PMC6683734
doi:
Substances chimiques
Guanine Nucleotide Exchange Factors
0
LTK protein, human
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2470-2480Informations de copyright
© 2019 Centonze et al.
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