Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (regulator of G-protein signaling) family members.
Serpentine Galphai-linked receptors support rapid adhesion and directed migration of leukocytes and other cell types. The intracellular mechanisms mediating and regulating chemoattractant-directed adhesion and locomotion are only now beginning to be explored. RGS (for regulator of G-protein signaling) proteins are a recently described family that regulate Galphai-stimulated pathways by acting as GTPase-activating proteins. Little is known about the GTPase activity of the Galphai proteins involved in adhesion and chemotaxis, or the significance of their regulation to these responses. Using transiently transfected lymphoid cells as a model system, we show that expression of RGS1, RGS3, and RGS4 inhibits chemoattractant-induced migration. In contrast, RGS2, a regulator of Galphaq activity, had no effect on cell migration to any chemoattractant. RGS1, RGS3, and RGS4 also reduced rapid chemoattractant-triggered adhesion, although the proadhesive response appears quantitatively less sensitive to RGS action than chemotaxis. The results suggest that the duration of the Galphai signal may be a particularly important parameter in the chemotactic responses of leukocytes, and demonstrate the potential for RGS family members to regulate cellular adhesive and migratory behaviors.
Laboratory of Immunology and Vascular Biology, Department of Pathology and Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, California 94305-5324, USA.
E P
EP
Bowman
J J
JJ
Campbell
K M
KM
Druey
A
A
Scheschonka
J H
JH
Kehrl
E C
EC
Butcher
D002448:Cell Adhesion; D002451:Cell Compartmentation; D018932:Chemokine CCL2 / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D016209:Interleukin-8 / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000166:cytology; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D020710:RGS Proteins; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D020690:GTPase-Activating Proteins; D016209:Interleukin-8; D011506:Proteins; D020710:RGS Proteins; C485898:RGS3 protein, human; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; C415085:Rgs3 protein, mouse; C098799:RGS4 protein; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go