title: c- Src and its role in cystic fibrosis.
abstract: Cystic fibrosis (CF) is a lethal inherited disease produced by mutations in the gene encoding the CFTR chloride channel. Loss of function in the CFTR gene is associated with a not much noticed increased expression and activity of the non-receptor protein-tyrosine kinase c-Src. CF is therefore the result from the loss of CFTR chloride transport function and its consequences, including a chronic and excessive c-Src signaling. On the other hand, c-Src, encoded by the SRC gene, is involved in diverse signaling mechanisms that regulate key cellular functions such as cell proliferation, apoptosis, oxidative stress, inflammation, and innate immunity. These c-Src-regulated cellular functions are also affected in CF; however, studies exploring a direct role of c-Src in the regulation of these cellular functions in CF are yet scarce and often controversial. Here we describe the c-Src regulation and functions, with emphasis in those altered in CF, and describe the role of CFTR as a "signaling molecule" that negatively modulates c-Src expression and activity. It is also discussed the emerging role of intracellular Cl-and IL-1β as intermediate signaling effectors between CFTR and c-Src.
authors.affiliation: Institute for Biomedical Research (BIOMED), Laboratory of Cellular and Molecular Biology, National Scientific and Technical Research Council (CONICET) and School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.
authors.forename: María Macarena
authors.initials: MM
authors.lastname: Massip Copiz
authors.affiliation: Institute for Biomedical Research (BIOMED), Laboratory of Cellular and Molecular Biology, National Scientific and Technical Research Council (CONICET) and School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina. Electronic address: tsantacoloma@gmail.com.
authors.forename: Tomás Antonio
authors.initials: TA
authors.lastname: Santa Coloma
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D003550:Cystic Fibrosis / Q000201:enzymology*; D006801:Humans; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: CFTR; Cystic fibrosis; IL-1β; IL1RN; Intracellular chloride; PP2; c-Src