Pseudomonas aeruginosa stimulates phosphorylation of the airway epithelial membrane glycoprotein Muc1 and activates MAP kinase.
We reported previously that Muc1 on the surface of epithelial cells was a receptor for Pseudomonas aeruginosa (Lillehoj EP, Kim BT, and Kim KC. Am J Physiol Lung Cell Mol Physiol 282: L751-L756, 2002). Other studies showed that the Muc1 cytoplasmic tail (CT) contains multiple phosphorylation sites, some of which are phosphorylated constitutively and associated with signaling proteins. However, the relationship between extracellular P. aeruginosa binding and intracellular signaling is unknown. To investigate the signaling mechanism of Muc1, this study examined phosphorylation of its CT and activation of the extracellular signal-regulated kinase (ERK) in response to stimulation by P. aeruginosa or purified flagellin. Our results showed 1) the Muc1 CT was phosphorylated constitutively on serine and tyrosine, 2) serine phosphorylation was stimulated by bacterial cells or flagellin, and 3) binding of P. aeruginosa or flagellin to Muc1 induced phosphorylation of ERK. These results are the first to demonstrate Muc1 CT phosphorylation and ERK activation in response to a clinically important airway pathogen.
Lillehoj
Erik P
EP
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
Kim
Hakryul
H
Chun
Ellen Y
EY
Kim
K Chul
KC
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D005944:Glucosamine / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011994:Recombinant Proteins; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D014162:Transfection
D018396:Mucin-1; D010710:Phosphates; D011994:Recombinant Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005944:Glucosamine