DYNACTIN PHOSPHORYLATION IS MODULATED IN RESPONSE TO CELLULAR EFFECTORS

Reversible protein phosphorylation has been implicated in the regulati on of organelle transport by cytoplasmic dynein. Motor function may be modulated directly by the phosphorylation of dynein or through the ph osphorylation of an accessory factor. Dynactin binds to cytoplasmic dy nein and is a required activator for dynein-driven vesicular motility. In metabolic labeling studies we have determined that the p150(Glued) subunit of dynactin is a phosphoprotein. Treatment of Rat2 cells with okadaic acid or with activators of protein kinase A or protein kinase C caused a marked increase in the incorporation of P-32 into p150(Glu ed); the increased phosphorylation correlated with activated vesicular transport. Phosphoamino-acid analysis of p150(Glued) isolated from ce lls treated with okadaic acid or with activators of either protein kin ase A or protein kinase C indicated exclusive labeling of phosphoserin e. These results suggest that the phosphorylation of dynactin may serv e to regulate intracellular transport catalyzed by cytoplasmic dynein. (C) 1997 Academic Press.