c-Src and its role in cystic fibrosis

MASSIP COPIZ MARÍA MACARENA; SANTA COLOMA T.A.

EUROPEAN JOURNAL OF CELL BIOLOGY

ELSEVIER GMBH

Año: 2016 vol. 95 p. 401 - 413

0171-9335

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, studiesexploring 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-1 as intermediate signaling effectors between CFTR and c-Src.