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

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.
Authors	Takeshi Sekiguchi, Nobuaki Furuno, Takashi Ishii, Eiji Hirose, Fumiko Sekiguchi, Yonggang Wang, Hideki Kobayashi
Journal	Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 24 Issue 2 Pg. 151-161 (Feb 2019) ISSN: 1365-2443 [Electronic] England
PMID	30570184 (Publication Type: Journal Article)
Copyright	© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
Chemical References	Cytoskeletal Proteins Hedgehog Proteins Intracellular Signaling Peptides and Proteins Multiprotein Complexes Proteins RRAGC protein, human WDR35 protein, human Mechanistic Target of Rapamycin Complex 1 RRAGA protein, human RRAGB protein, human Monomeric GTP-Binding Proteins
Topics	Cytoskeletal Proteins HEK293 Cells Hedgehog Proteins Humans Intracellular Signaling Peptides and Proteins Lysosomes (metabolism) Mechanistic Target of Rapamycin Complex 1 (genetics, metabolism) Monomeric GTP-Binding Proteins (genetics, metabolism) Multiprotein Complexes (genetics, metabolism) Phosphorylation Protein Binding Protein Interaction Domains and Motifs Proteins (genetics, metabolism) Signal Transduction Two-Hybrid System Techniques

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