
The signaling adaptor p62 is a critical mediator of important cellular functions, owing to its ability to establish interactions with various signaling intermediaries. Here, we identify raptor as an interacting partner of p62. Thus, p62 is an integral part of the mTORC1 complex and is necessary to mediate amino acid signaling for the activation of S6K1 and 4EBP1. p62 interacts in an amino acid-dependent manner with mTOR and raptor. In addition, p62 binds the Rags proteins and favors formation of the active Rag heterodimer that is further stabilized by raptor. Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation.
Intracellular Signaling Peptides and Proteins, Proteins, Cell Biology, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, GTP Phosphohydrolases, Mice, HEK293 Cells, Multiprotein Complexes, Sequestosome-1 Protein, Autophagy, NIH 3T3 Cells, Animals, Humans, Carrier Proteins, Lysosomes, Molecular Biology, Dimerization, Heat-Shock Proteins, Protein Kinase C, Adaptor Proteins, Signal Transducing, Plasmids
Intracellular Signaling Peptides and Proteins, Proteins, Cell Biology, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, GTP Phosphohydrolases, Mice, HEK293 Cells, Multiprotein Complexes, Sequestosome-1 Protein, Autophagy, NIH 3T3 Cells, Animals, Humans, Carrier Proteins, Lysosomes, Molecular Biology, Dimerization, Heat-Shock Proteins, Protein Kinase C, Adaptor Proteins, Signal Transducing, Plasmids
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