REGULATION OF CHEMOTACTIC AND PROADHESIVE RESPONSES TO CHEMOATTRACTANT RECEPTORS BY RGS (REGULATOR OF G-PROTEIN SIGNALING) FAMILY MEMBERS

Serpentine G alpha(i)-linked receptors support rapid adhesion and dire cted migration of leukocytes and other cell types. The intracellular m echanisms mediating and regulating chemoattractant-directed adhesion a nd locomotion are only now beginning to be explored. RGS (for regulato r of G-protein signaling) proteins are a recently described family tha t regulate G alpha(i)-stimulated pathways by acting as GTPase-activati ng proteins. Little is known about the GTPase activity of the G alpha( i) proteins involved in adhesion and chemotaxis, or the significance o f their regulation to these responses. Using transiently transfected l ymphoid cells as a model system, we show that expression of RGS1, RGS3 , and RGS4 inhibits chemoattractant-induced migration. In contrast, RG S2, a regulator of G alpha(q) activity, had no effect on cell migratio n to any chemoattractant. RGS1, RGS3, and RGS4 also reduced rapid chem oattractant-triggered adhesion, although the proadhesive response appe ars quantitatively less sensitive to RGS action than chemotaxis, The r esults suggest that the duration of the G alpha(i) signal may be a par ticularly important parameter in the chemotactic responses of leukocyt es, and demonstrate the potential for RGS family members to regulate c ellular adhesive and migratory behaviors.