ArticleScientific reports2016
Akt mediated phosphorylation of LARP6; critical step in biosynthesis of type I collagen.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- An intrinsically disordered region mediates RNA-binding selectivity and cellular activities of LARP6.Nature communications · 2026Article
- Noncanonical RNA binding of human La-related protein 6.Nucleic acids research · 2025Article
- IGF-1 regulates LARP6-mediated collagen metabolism in vaginal fibroblasts of POP patients via the PI3K/AKT pathway.Scientific reports · 2025Article
- Article
- A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6.ACS omega · 2025Article
- Post-translational modifications of collagen and its related diseases in metabolic pathways.Acta pharmaceutica Sinica. B · 2025Review
- Piezo1 Activation Drives Enhanced Collagen Synthesis in Aged Animal Skin Induced by Poly L-Lactic Acid Fillers.International journal of molecular sciences · 2024Article
- Characterization of Sequence-Specific Binding of LARP6 to the 5' Stem-Loop of Type I Collagen mRNAs and Implications for Rational Design of Antifibrotic Drugs.Journal of molecular biology · 2022Article
- Imaging of type I procollagen biosynthesis in cells reveals biogenesis in highly organized bodies; Collagenosomes.Matrix biology plus · 2021Article
- Cromolyn platform suppresses fibrosis and inflammation, promotes microglial phagocytosis and neurite outgrowth.Scientific reports · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Discovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.ACS medicinal chemistry letters · 2021Article
- β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells.Scientific reports · 2020Article
- Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen.Annals of surgery · 2020Article
- GORAB promotes embryonic lung maturation through antagonizing AKT phosphorylation, versican expression, and mesenchymal cell migration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Signal Transduction in Ribosome Biogenesis: A Recipe to Avoid Disaster.International journal of molecular sciences · 2019Review
- Parity predisposes breasts to the oncogenic action of PAPP-A and activation of the collagen receptor DDR2.Breast cancer research : BCR · 2019Article
- l-Proline Alleviates Kidney Injury Caused by AFB1 and AFM1 through Regulating Excessive Apoptosis of Kidney Cells.Toxins · 2019Article
- Discovery and evaluation of inhibitor of LARP6 as specific antifibrotic compound.Scientific reports · 2019Article
- The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating L-Proline and Downstream Apoptosis.BioMed research international · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
La ribonucleoprotein domain family, member 6 (LARP6) is the RNA binding protein, which regulates translation of collagen mRNAs and synthesis of type I collagen. Posttranslational modifications of LARP6 and how they affect type I collagen synthesis have not been studied. We show that in lung fibroblasts LARP6 is phosphorylated at 8 serines, 6 of which are located within C-terminal domain. Phosphorylation of LARP6 follows a hierarchical order; S451 phosphorylation being a prerequisite for phosphorylations of other serines. Inhibition of PI3K/Akt pathway reduced the phosphorylation of LARP6, but had no effect on the S451A mutant, suggesting that PI3K/Akt pathway targets S451 and we have identified Akt as the responsible kinase. Overexpression of S451A mutant had dominant negative effect on collagen biosynthesis; drastically reduced secretion of collagen and induced hyper-modifications of collagen α2 (I) polypeptides. This indicates that LARP6 phosphorylation at S451 is critical for regulating translation and folding of collagen polypeptides. Akt inhibitor, GSK-2141795, which is in clinical trials for treatment of solid tumors, reduced collagen production by human lung fibroblasts with EC50 of 150 nM. This effect can be explained by inhibition of LARP6 phosphorylation and suggests that Akt inhibitors may be effective in treatment of various forms of fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.