RAPID INTERNALIZATION OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR REQUIRES PHOSPHORYLATED SERINE-726

S726 of the cytoplasmic domain of the polymeric immunoglobulin recepto r (pIgR) resides within a consensus sequence for phosphorylation by pr otein kinases A, G, and C, and casein kinase II. Mutation of S726 to A la and expression of this mutant pIgR in Madin-Darby canine kidney cel ls results in a receptor in which steady-state phosphorylation is redu ced to 49% of wild-type levels. This mutant receptor is also significa ntly impaired in its internalization from the basolateral membrane. Du ring the first minute, internalization of radioiodinated ligands (eith er dIgA or monovalent anti-pIgR Fabs) by this mutant pIgR is only 35% of that by wild-type pIgR. Internalization of unoccupied mutant recept ors is similarly inhibited. Delivery of newly made mutant receptor fro m the trans-Golgi network to the basolateral surface is completely nor mal. The only other trafficking step inhibited by this mutation is the transcytosis of radioiodinated dIgA Within 2 h, the mutant pIgR will transcytose 58% of a preinternalized cohort of dIgA, while the wild-ty pe transcytoses 76%. This inhibition of transcytosis may be an indirec t consequence of impaired internalization. The correlation between the loss of phosphorylation and inhibition of internalization suggests th at phosphorylation of S726 may represent a novel mechanism for regulat ion of internalization of the pIgR.