Evidence map›Paper›PMID 26438830›Full record

ArticleThe Journal of cell biology2015

Growth factor signaling to mTORC1 by amino acid-laden macropinosomes.

Sei Yoshida, Regina Pacitto, Yao Yao, Ken Inoki, Joel A Swanson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
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  4. Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025
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  15. Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles.Proceedings of the National Academy of Sciences of the United States of America · 2023
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Sei YoshidaDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109.
Regina PacittoDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109.
Yao YaoDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.
Ken InokiDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.
Joel A SwansonDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 jswan@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Role of TSC-mTORC1 pathway for podocyte injury in diabetic nephropathyR01DK083491 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI INOKI, KEN · 2009 to 2017
$3.0M
Lysosomal cholesterol-dependent anabolic regulationR01DK124709 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI INOKI, KEN · 2022 to 2025
$2.1M
The Regulation of MacropinocytosisR01GM110215 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SWANSON, JOEL A · 2014 to 2017
$1.3M
NIDDK NIH HHS R01 DK083491NIDDK NIH HHS R01-DK-083491NIDDK NIH HHS R01 DK124709NIGMS NIH HHS R01 GM110215NIGMS NIH HHS R01-GM-110215-01
6 · The paper itself

Abstract

The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid-dependent activation of mTORC1. Here, we show that growth factor-dependent activation of mTORC1 by amino acids, but not glucose, requires macropinocytosis. In murine bone marrow-derived macrophages and murine embryonic fibroblasts stimulated with their cognate growth factors or with phorbol myristate acetate, activation of mTORC1 required an Akt-independent vesicular pathway of amino acid delivery into endolysosomes, mediated by the actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase solutes into endolysosomes sufficiently fast to explain growth factor-mediated signaling by amino acids. Therefore, the amino acid-laden macropinosome is an essential and discrete unit of growth factor receptor signaling to mTORC1.

Indexed as

PinocytosisAmino AcidsAnimalsBiological TransportEndosomesFibroblastsHEK293 CellsHumansMacrophage Colony-Stimulating FactorMacrophagesMechanistic Target of Rapamycin Complex 1Mice, Inbred C57BLMultiprotein ComplexesPlatelet-Derived Growth FactorSignal TransductionTOR Serine-Threonine KinasesAmino AcidsMacrophage Colony-Stimulating FactorMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesPlatelet-Derived Growth FactorTOR Serine-Threonine Kinases

Identifiers

PMID26438830
PMCPMC4602043
OpenAlexW2179272349

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.