Opposing roles of PAK2 and PAK4 in synergistic induction of MUC5AC mucin by bacterium NTHi and EGF.
Mucin, a major component of mucus, plays a critical role in host mucosal defense response by participating in mucociliary clearance. However, if overproduced, overproduced mucus leads to airway mucus obstruction and conductive hearing loss. Despite extensive studies that focus on investigating how MUC5AC mucin is regulated by one inducer at a time, how MUC5AC is synergistically regulated by multiple factors remains unknown. Here we provide direct evidence for the first time that bacterial pathogen NTHi and human growth factor EGF synergize with each other to potently up-regulate MUC5AC mucin transcription. Moreover, activation of both p38 and ERK is required for synergistic induction of MUC5AC by NTHi and EGF. Finally, PAK2 and PAK4 are differentially involved in this synergistic induction of MUC5AC by acting upstream of p38 and ERK. Our studies bring novel insights into our understanding of synergistic regulation of MUC5AC mucin by both pathological and physiological inducers.
Huang
Yuxian
Y
Department of Microbiology & Immunology, Box 672, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Mikami
Fumi
F
Jono
Hirofumi
H
Zhang
Wenhong
W
Weng
Xinhua
X
Koga
Tomoaki
T
Xu
Haidong
H
Yan
Chen
C
Kai
Hirofumi
H
Li
Jian-Dong
JD
D002457:Cell Extracts / Q000494:pharmacology; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006193:Haemophilus influenzae / Q000145:classification / Q000502:physiology*; D006801:Humans; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002457:Cell Extracts; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D004815:Epidermal Growth Factor; C116367:PAK4 protein, human; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases