Rapid internalization of the polymeric immunoglobulin receptor requires phosphorylated serine 726.
S726 of the cytoplasmic domain of the polymeric immunoglobulin receptor (pIgR) resides within a consensus sequence for phosphorylation by protein kinases A, G, and C, and casein kinase II. Mutation of S726 to Ala and expression of this mutant pIgR in Madin-Darby canine kidney cells results in a receptor in which steady-state phosphorylation is reduced to 49% of wild-type levels. This mutant receptor is also significantly impaired in its internalization from the basolateral membrane. During the first minute, internalization of radioiodinated ligands (either dIgA or monovalent anti-pIgR Fabs) by this mutant pIgR is only 35% of that by wild-type pIgR. Internalization of unoccupied mutant receptors is similarly inhibited. Delivery of newly made mutant receptor from the trans-Golgi network to the basolateral surface is completely normal. 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-type transcytoses 76%. This inhibition of transcytosis may be an indirect consequence of impaired internalization. The correlation between the loss of phosphorylation and inhibition of internalization suggests that phosphorylation of S726 may represent a novel mechanism for regulation of internalization of the pIgR.
Okamoto
C T
CT
Department of Anatomy, University of California, San Francisco 94143-0452.
Song
W
W
Bomsel
M
M
Mostov
K E
KE
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004285:Dogs; D004705:Endocytosis; D007668:Kidney; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D010768:Phosphoserine; D017354:Point Mutation; D011817:Rabbits; D011961:Receptors, Fc / Q000096:biosynthesis / Q000378:metabolism*; D012694:Serine; D014162:Transfection
D046911:Macromolecular Substances; D011961:Receptors, Fc; D010768:Phosphoserine; D012694:Serine