Evidence map›Paper›PMID 12782713›Full record

ArticleThe Journal of experimental medicine2003

MIF signal transduction initiated by binding to CD74.

Lin Leng, Christine N Metz, Yan Fang, Jing Xu, Seamas Donnelly, John Baugh, Thomas Delohery, Yibang Chen, Robert A Mitchell, Richard Bucala

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 574 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
574citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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

574 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,107 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Article
  5. Identification of Ferro-Aging-Related Biomarkers for Ulcerative Colitis Through Integrated Machine Learning, Single-Cell Analysis, and Spatial Transcriptomics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  7. International journal of molecular sciences · 2026
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  14. Crystal structure of Plasmodium vivax macrophage migration inhibitory factor.Acta crystallographica. Section F, Structural biology communications · 2026
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514 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

10 authors at 5 institutions in 2 countries.

Lin LengDepartment of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208031, New Haven, CT 06520-8031, USA.
Christine N Metz
Yan Fang
Jing Xu
Seamas Donnelly
John Baugh
Thomas Delohery
Yibang Chen
Robert A Mitchell
Richard Bucala
Yale University · USUniversity College Dublin · IEIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · USUniversity of Louisville · US

Funding

Mechanisms of Rheumatoid Synovial Fibroblast ActivationR01AR049610 · NIAMS · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2002 to 2018
$5.0M
MIF AND THE HOST RESPONSE TO INFECTIONR01AI042310 · NIAID · YALE UNIVERSITY · PI BUCALA, RICHARD J · 1998 to 2013
$4.3M
NIAID NIH HHS 1R01AI42310NIAID NIH HHS R01 AI042310NIAMS NIH HHS 1RO1AR49610NIAMS NIH HHS R01 AR049610Wellcome Trust
6 · The paper itself

Abstract

Macrophage migration inhibitory factor (MIF) accounts for one of the first cytokine activities to have been described, and it has emerged recently to be an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. The protein is encoded by a unique but highly conserved gene, and X-ray crystallography studies have shown MIF to define a new protein fold and structural superfamily. Although recent work has begun to illuminate the signal transduction pathways activated by MIF, the nature of its membrane receptor has not been known. Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF. MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal-regulated kinase-1/2 MAP kinase cascade, cell proliferation, and PGE2 production. A recombinant, soluble form of CD74 binds MIF with a dissociation constant of approximately 9 x 10-9 Kd, as defined by surface plasmon resonance (BIAcore analysis), and soluble CD74 inhibits MIF-mediated extracellular signal-regulated kinase activation in defined cell systems. These data provide a molecular basis for MIF's interaction with target cells and identify it as a natural ligand for CD74, which has been implicated previously in signaling and accessory functions for immune cell activation.

Indexed as

AnimalsAntigens, Differentiation, B-LymphocyteApoptosisCloning, MolecularGene ExpressionHistocompatibility Antigens Class IIHumansIn Vitro TechniquesMacrophage Migration-Inhibitory FactorsMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMonocytesAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIinvariant chainMacrophage Migration-Inhibitory FactorsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesRecombinant Proteins

Identifiers

PMID12782713
PMCPMC2193907
OpenAlexW2161048718

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.