The laminin receptor modulates granulocyte-macrophage colony-stimulating factor receptor complex formation and modulates its signaling Journal Article


Authors: Chen, J.; Cárcamo, J. M.; Borquez-Ojeda, O.; Erdjument-Bromage, H.; Tempst, P.; Golde, D. W.
Article Title: The laminin receptor modulates granulocyte-macrophage colony-stimulating factor receptor complex formation and modulates its signaling
Abstract: Basement membrane matrix proteins are known to up-regulate granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in neutrophils and mononuclear phagocytes, but the mechanisms involved are poorly understood. We used the intracellular portion of the α subunit of the GM-CSF receptor (αGMR) to search for interacting proteins and identified the 67-kDa laminin receptor (LR), a nonintegrin matrix protein receptor expressed in several types of host defense cells and certain tumors, as a binding partner. LR was found to interact with the β subunit of the GMR (βGMR) as well. Whereas GM-CSF functions by engaging the αGMR and βGMR into receptor complexes, LR inhibited GM-CSF-induced receptor complex formation. Laminin and fibronectin binding to LR was found to prevent the binding of βGMR to LR and relieved the LR inhibition of GMR. These findings provide a mechanistic basis for enhancing host defense cell responsiveness to GM-CSF at transendothelial migration sites while suppressing it in circulation.
Keywords: signal transduction; mitogen activated protein kinase; protein phosphorylation; human cell; complex formation; protein protein interaction; cell line; kinetics; gamma interferon; base sequence; neutrophils; immunomodulation; models, molecular; protein structure, tertiary; binding sites; molecular interaction; protein subunits; cytokine release; stat5 protein; molecular weight; laminin; macromolecular substances; dna, complementary; fibronectin; granulocyte-macrophage colony-stimulating factor; fibronectins; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor; humans; human; priority journal; article; laminin receptor; receptors, laminin
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 100
Issue: 24
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2003-11-25
Start Page: 14000
End Page: 14005
Language: English
DOI: 10.1073/pnas.2334584100
PUBMED: 14614142
PROVIDER: scopus
PMCID: PMC283535
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. David Golde
    127 Golde
  2. Juan O Carcamo
    31 Carcamo
  3. Paul J Tempst
    324 Tempst