InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MLST8

Summary

InnateDB Protein

IDBP-10144.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MLST8

Protein Name

MTOR associated protein, LST8 homolog (S. cerevisiae)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000371888

InnateDB Gene

IDBG-10142 (MLST8)

Protein Structure

UniProt Annotation

Function

Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1- mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient- poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum- induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. {ECO:0000269PubMed:12718876, ECO:0000269PubMed:15467718}.

Subcellular Localization

Cytoplasm {ECO:0000250}.

Disease Associations

Tissue Specificity

Broadly expressed, with highest levels in skeletal muscle, heart and kidney. {ECO:0000269PubMed:12408816}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 46 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	46 [view]
Protein-Protein	46 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological Process

GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0031295	T cell costimulation
GO:0032008	positive regulation of TOR signaling
GO:0032956	regulation of actin cytoskeleton organization
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling