LTK is an ER-resident receptor tyrosine kinase that regulates secretion

Federica G. Centonze, Veronika Reiterer, Karsten Nalbach, Kota Saito, Krzysztof Pawlowski, Christian Behrends, Hesso Farhan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2470-2480
Number of pages11
JournalJournal of Cell Biology
Volume218
Issue number8
DOIs
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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