Tyrosine kinase c-Src constitutes a bridge between CFTR channel failure and MUC1 overexpression in cystic fibrosis

GONZÁLEZ-GUERRICO AM.; CAFFERATA EG; RADRIZZANI M; MARCUCCI F; GRUENERT D.; PIVETTA OH; FAVALORO RR; LAGUENS R; PERRONE SV; GALLO GC; SANTA COLOMA TA

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2002 vol. 277 p. 17239 - 17247

0021-9258

Cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) chloride channel, is associated in the respiratory system with the accumulation of mucus and impaired lung function. The role of the CFTR channel in the regulation of the intracellular pathways that determine the overexpression of mucin genes is unknown. Using differential display, we have observed the differential expression of several mRNAs that may correspond to putative CFTR-dependent genes. One of these mRNAs was further characterized, and it corresponds to the tyrosine kinase c-Src. Additional results suggest that c-Src is a central element in the pathway connecting the CFTR channel with MUC1 overexpression and that the overexpression of mucins is a primary response to CFTR malfunction in cystic fibrosis, which occurs even in the absence of bacterial infection