RGS1 is expressed in monocytes and acts as a GTPase-activating protein forG-protein-coupled chemoattractant receptors

The leukocyte response to chemoattractants is transduced by the interaction of transmembrane receptors with GTP-binding regulatory proteins (G-protein s). RGS1 is a member of a protein family constituting a newly appreciated a nd large group of proteins that act as deactivators of G-protein signaling pathways by accelerating the GTPase activity of G-protein alpha subunits. W e demonstrate here that RGS1 is expressed in human monocytes; by immunofluo rescence and subcellular fractionation RGS1 was localized to the plasma mem brane. By using a mixture of RGS1 and plasma membranes, we were able to dem onstrate GAP activity of RGS1 on receptor-activated G-proteins; RGS1 did no t affect ligand-stimulated GDP-GTP exchange;We found that RGS1 desensitizes a variety of chemotactic receptors including receptors for N-formyl-methio nyl-leucylphenylalanine, leukotriene B4, and C5a. Interaction of RGS protei ns and ligand-induced G-protein signaling can be demonstrated by determinin g GTPase activity using purified RGS proteins and plasma membranes.