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.
LTK is an ER-resident receptor tyrosine kinase that regulates secretion
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Federica G. Centonze, Veronika Reiterer, Karsten Nalbach, Kota Saito, Krzysztof Pawlowski, Christian Behrends, Hesso Farhan; LTK is an ER-resident receptor tyrosine kinase that regulates secretion. J Cell Biol 5 August 2019; 218 (8): 2470–2480. doi: https://doi.org/10.1083/jcb.201903068
Download citation file: