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

AUTOR(ES)

Chen, Jian

FONTE

National Academy of Sciences

RESUMO

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.

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