The SRC family protein tyrosine kinase p62(yes) controls polymeric IgA transcytosis in vivo

Transcytosis of polymeric immunoglobulin A (pIgA) across epithelial cells i s mediated by the polymeric immunoglobulin receptor (pIgR). Binding of pIgA to pIgR stimulates transcytosis of the pIgA-pIgR complex via a signal tran sduction pathway that is dependent on a protein tyrosine kinase (PTK) of th e SRC family. Here we identify the PTK as p62(yes). We demonstrate the spec ific physical and functional association of the pIgR with p62(yes) in roden t liver. Analysis of p62(yes) knockout mice revealed a dramatic reduction i n the association of tyrosine kinase activity with the pIgR and in transcyt osis of pIgA. We conclude that p62(yes) controls pIgA transcytosis in vivo.