The SRC family protein tyrosine kinase p62yes controls polymeric IgA transcytosis in vivo.
Transcytosis of polymeric immunoglobulin A (pIgA) across epithelial cells is mediated by the polymeric immunoglobulin receptor (pIgR). Binding of pIgA to pIgR stimulates transcytosis of the pIgA-pIgR complex via a signal transduction pathway that is dependent on a protein tyrosine kinase (PTK) of the SRC family. Here we identify the PTK as p62yes. We demonstrate the specific physical and functional association of the pIgR with p62yes in rodent liver. Analysis of p62yes knockout mice revealed a dramatic reduction in the association of tyrosine kinase activity with the pIgR and in transcytosis of pIgA. We conclude that p62yes controls pIgA transcytosis in vivo.
Luton
F
F
Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Vergés
M
M
Vaerman
J P
JP
Sudol
M
M
Mostov
K E
KE
D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D001692:Biological Transport; D060748:Fetuins; D007070:Immunoglobulin A / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics; D011233:Precipitin Tests; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051575:Proto-Oncogene Proteins c-yes; D051381:Rats; D017207:Rats, Sprague-Dawley; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism; D015398:Signal Transduction; D000509:alpha-Fetoproteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D001212:Asialoglycoproteins; D060748:Fetuins; D007070:Immunoglobulin A; D011518:Proto-Oncogene Proteins; D019056:Receptors, Polymeric Immunoglobulin; D000509:alpha-Fetoproteins; C017029:asialofetuin; C034639:polymeric IgA; D015688:Oncogene Protein pp60(v-src); D051575:Proto-Oncogene Proteins c-yes; C496639:Yes1 protein, mouse; D019061:src-Family Kinases