The laminin receptor modulates granulocyte-macrophage colony-stimulating factor receptor complex formation and modulates its signaling.
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 alpha subunit of the GM-CSF receptor (alphaGMR) 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 (betaGMR) as well. Whereas GM-CSF functions by engaging the alphaGMR and betaGMR into receptor complexes, LR inhibited GM-CSF-induced receptor complex formation. Laminin and fibronectin binding to LR was found to prevent the binding of betaGMR 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.
Chen
Jian
J
Department of Pharmacology, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.
Cárcamo
Juan M
JM
Bórquez-Ojeda
Oriana
O
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Golde
David W
DW
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005353:Fibronectins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017474:Receptors, Laminin / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D018076:DNA, Complementary; D005353:Fibronectins; D007797:Laminin; D046911:Macromolecular Substances; D021122:Protein Subunits; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D017474:Receptors, Laminin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor