期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：14000-14005
DOI：10.1073/pnas.2334584100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 subunit of the GM-CSF receptor (GMR) 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 {beta} subunit of the GMR ({beta}GMR) as well. Whereas GM-CSF functions by engaging the GMR and {beta}GMR into receptor complexes, LR inhibited GM-CSF-induced receptor complex formation. Laminin and fibronectin binding to LR was found to prevent the binding of {beta}GMR 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.
