Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis.
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.
González-Guerrico
Anatilde M
AM
Instituto de Investigaciones Bioquimicas Fundación Campomar (UBA, CONICET), 1405 Buenos Aires, Argentina.
Cafferata
Eduardo G
EG
Radrizzani
Martí
M
Marcucci
Florencia
F
Gruenert
Dieter
D
Pivetta
Omar H
OH
Favaloro
Roberto R
RR
Laguens
Rubén
R
Perrone
Sergio V
SV
Gallo
Guillermo C
GC
Santa-Coloma
Tomás A
TA
D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003001:Cloning, Molecular; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005799:Genes, Dominant; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000378:metabolism; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
C505032:CFTR protein, human; D018396:Mucin-1; D009077:Mucins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D016392:Proto-Oncogene Proteins pp60(c-src)