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 |