title: TPL2 signalling: from Toll-like receptors-mediated ERK1/ERK2 activation to Cystic Fibrosis lung disease.
abstract: Cystic Fibrosis (CF) is the most common lethal genetic recessive disorder, with a carrier frequency of 1 in 27 among North American Caucasians. Mitogen-activated protein kinases (MAPKs) and pro-inflammatory cytokines have crucial functions in the innate immune response of epithelial cells. They determine the inflammation status and the host response to pathogenic infections. However, in CF, bacterial-driven inflammation leads to tissue destruction, reduction in lung function and mortality. Recognition of invading pathogens is mediated in part by Toll-like receptors (TLR) activation of intracellular signalling cascade leading to cytokines' synthesis. The protein kinase Tumour Progression Locus 2 (TPL2) is a key molecule in relaying inflammatory stimuli to ERK1/ERK2 MAPKs. In this review, we summarized the recent findings on TPL2 signalling and how TPL2 can contribute to the excessive inflammation found in CF. Pharmacologically targeting this kinase could have a significant benefit for CF patients dealing with chronic bacterial infections such as Pseudomonas aeruginosa. This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances.
authors: Meakins-Christie Laboratories, McGill University Health Centre Research Institute, Montreal, Canada.
authors: Guy
authors: G
authors: Martel
authors: Meakins-Christie Laboratories, McGill University Health Centre Research Institute, Montreal, Canada. Electronic address: simon.rousseau@mcgill.ca.
authors: Simon
authors: S
authors: Rousseau
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; D051193:Toll-Like Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020930:MAP Kinase Kinase Kinases
keywords: Cystic Fibrosis; Inflammation; MAPK; Pseudomonas aeruginosa; TPL2