INVESTIGADORES
KORNBLIHTT Alberto Rodolfo
artículos
Título:
Cross-talk between signaling pathways regulates alternative splicing: a novel role for JNK
Autor/es:
PELISCH, F; BLAUSTEIN, M; KORNBLIHTT, A; SREBROW, A
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Referencias:
Año: 2005 vol. 280 p. 25461 - 25469
ISSN:
0021-9258
Resumen:
The regulation of alternative splicing by extracellularsignals represents a key event in the control of geneexpression. There is increasing evidence showing thatmany extracellular cues regulate alternative splicing.Nevertheless, the broad picture regarding the role ofdifferent signaling pathways and their interaction remainsincomplete. Using the fibronectin gene as amodel, we show that a laminin-rich basement membraneregulates the alternative splicing of two out of threeregions of the transcript (extra domain I and typeIII connecting segment) in mammary epithelial cells,through a non-stress c-Jun N-terminal kinase (JNK) signalingpathway. We propose that dephosphorylation ofthe extracellular signal-regulated kinase is involved inthis regulatory process. Furthermore, the laminin-richbasement membrane blocks the effect of a mammarymesenchymal cell-conditioned medium, which stimulatesthe inclusion of extra domain I and type III connectingsegmentthroughaphosphatidylinositol3-kinasedependentcascade, indicating that JNK signalingcan inhibit the phosphatidylinositol 3-kinase-mediatedsplicing regulation. These results implicate JNK in theregulation of alternative splicing and provide new evidenceon how extracellular stimuli are converted intochanges in splicing patterns, strengthening the viewthat the control of alternative splicing is as complex andrelevant as transcriptional control, together accountingfor the spatiotemporal requirements of gene expression.