Bowman, EP; Campbell, JJ; Druey, KM; Scheschonka, A; Kehrl, JH; Butcher, EC

Journal of Biological Chemistry [J. Biol. Chem.], vol. 273, no. 43, pp. 28040-28048, 23 Oct 1998

Serpentine G alpha sub(i)-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 G alpha sub(i)-stimulated pathways by acting as GTPase-activating proteins. Little is known about the GTPase activity of the G alpha sub(i) 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 G alpha sub(q) 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 G alpha sub(i) 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.