Lillehoj Erik P, Kim Hakryul, Chun Ellen Y, Kim K Chul
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L809-15. doi: 10.1152/ajplung.00385.2003. Epub 2004 Jun 25.
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.
我们先前报道过，上皮细胞表面的Muc1是铜绿假单胞菌的受体（Lillehoj EP、Kim BT和Kim KC。《美国生理学杂志：肺细胞与分子生理学》282：L751-L756，2002年）。其他研究表明，Muc1胞质尾（CT）含有多个磷酸化位点，其中一些位点持续磷酸化并与信号蛋白相关。然而，细胞外铜绿假单胞菌结合与细胞内信号传导之间的关系尚不清楚。为了研究Muc1的信号传导机制，本研究检测了其CT的磷酸化以及细胞外信号调节激酶（ERK）在铜绿假单胞菌或纯化鞭毛蛋白刺激下的激活情况。我们的结果表明：1）Muc1 CT在丝氨酸和酪氨酸上持续磷酸化；2）细菌细胞或鞭毛蛋白刺激丝氨酸磷酸化；3）铜绿假单胞菌或鞭毛蛋白与Muc1的结合诱导ERK磷酸化。这些结果首次证明了Muc1 CT磷酸化和ERK激活是对一种临床上重要的气道病原体的反应。
