Evidence map›Paper›PMID 9032279›Full record

ArticleMolecular and cellular biology1997

Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells.

J C Brüning, J Winnay, B Cheatham, C R Kahn

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 1997. 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
12.9field-weighted citation impact, top 1% 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, 212 citations in OpenAlex.

  1. Trial
  2. Targeting the Aryl Hydrocarbon Receptor to Attenuate IGF1R Signaling in Thyroid Eye Disease.Thyroid : official journal of the American Thyroid Association · 2025
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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

4 authors at 1 institution in 1 country.

J C BrüningJoslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Winnay
B Cheatham
C R Kahn
Joslin Diabetes Center · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5M
Insulin Receptor Substrates and Insulin ActionR01DK033201 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 1986 to 2016
$10.6M
NIDDK NIH HHS DK 33201NIDDK NIH HHS P30 DK36836
6 · The paper itself

Abstract

Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin-like growth factor 1 (IGF-1) and insulin (E. Araki et al., Nature 372:186-190, 1994; H. Tamemoto et al., Nature 372:182-186, 1994). Embryonic fibroblasts and 3T3 cell lines derived from IRS-1-deficient embryos exhibit no IGF-1-stimulated IRS-1 phosphorylation or IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity but exhibit normal phosphorylation of IRS-2 and Shc and normal IRS-2-associated PI 3-kinase activity. IRS-1 deficiency results in a 70 to 80% reduction in IGF-1-stimulated cell growth and parallel decreases in IGF-1-stimulated S-phase entry, PI 3-kinase activity, and induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases ERK 1 and ERK 2. Expression of IRS-1 in IRS-1-deficient cells by retroviral gene transduction restores IGF-1-stimulated mitogenesis, PI 3-kinase activation, and c-fos and egr-1 induction in proportion to the level of reconstitution. Increasing the level of IRS-2 in these cells by using a retrovirus reconstitutes IGF-1 activation of PI 3-kinase and immediate-early gene expression to the same degree as expression of IRS-1; however, IRS-2 overexpression has only a minor effect on IGF-1 stimulation of cell cycle progression. These results indicate that IRS-1 is not necessary for activation of ERK 1 and ERK 2 and that activation of ERK 1 and ERK 2 is not sufficient for IGF-1-stimulated activation of c-fos and egr-1. These data also provide evidence that IRS-1 and IRS-2 are not functionally interchangeable signaling intermediates for stimulation of mitogenesis despite their highly conserved structure and many common functions such as activating PI 3-kinase and early gene expression.

Indexed as

Adaptor Proteins, Signal TransducingImmediate-Early Proteins3T3 CellsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell LineDNA-Binding ProteinsEarly Growth Response Protein 1Enzyme ActivationFibroblastsGene Expression RegulationGenes, fosGenes, Immediate-EarlyGene Transfer TechniquesGRB2 Adaptor ProteinHumansAdaptor Proteins, Signal TransducingCalcium-Calmodulin-Dependent Protein KinasesDNA-Binding ProteinsEarly Growth Response Protein 1EGR1 protein, humanEgr1 protein, mouseGRB2 Adaptor ProteinGRB2 protein, humanGrb2 protein, mouseImmediate-Early ProteinsInsulin-Like Growth Factor IInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIRS1 protein, humanIrs1 protein, mouseIRS2 protein, humanIrs2 protein, mousePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)ProteinsTranscription Factors

Identifiers

PMID9032279
PMCPMC231877
OpenAlexW2139907742

What OpenQuestion holds

Textmetadata
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.