RagA, an mTORC1 activator, interacts with a hedgehog signaling protein, WDR35/IFT121

Takeshi Sekiguchi, Nobuaki Furuno, Takashi Ishii, Eiji Hirose, Fumiko Sekiguchi, Yonggang Wang, Hideki Kobayashi

Research output: Contribution to journalArticle

Abstract

Small Ras-like GTPases act as molecular switches for various signal transduction pathways. RagA, RagB/RagC and RagD are small Ras-like GTPases that play regulatory roles in mTORC1. Lack of proper activation of mTORC1 can lead to diseases, such as cancer and diabetes. In this study, we found an interaction between RagA and WDR35. Mutations of WDR35 may cause genetic diseases including Sensenbrenner syndrome. WDR35 seems to be a hedgehog signaling protein with a possible ciliary function and a possible upstream regulator of RagA. RagB is a homologue of RagA and is also associated with WDR35. WDR35 is present in the endoplasmic reticulum, but usually not in lysosomes, where Rag family proteins act as an mTORC1 switch. Over-expression of WDR35 results in decreased phosphorylation of ribosome S6 protein in a RagA-, RagB- and RagC-dependent manner. Thus, WDR35 is associated with RagA, RagB and RagC and might negatively influence mTORC1 activity.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalGenes to Cells
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Sekiguchi, T., Furuno, N., Ishii, T., Hirose, E., Sekiguchi, F., Wang, Y., & Kobayashi, H. (2019). RagA, an mTORC1 activator, interacts with a hedgehog signaling protein, WDR35/IFT121. Genes to Cells, 24(2), 151-161. https://doi.org/10.1111/gtc.12663