Src family kinases are central regulators of a large number of signaling pathways. To adapt to the idiosyncrasies of different cell types, these kinases may need a fine-tuning of their intrinsic molecular control mechanisms. Here, we describe on a molecular level how the Fyn kinase uses alternative splicing to adapt to different cellular environments. Using structural analysis, site-directed mutagenesis, and functional analysis, we show how the inclusion of either exon 7A or 7B affects the autoinhibition of Fyn and how this changes the SH3-dependent interaction and tyrosine phosphorylation of Sam68, with functional consequences for the Sam68-regulated survival of epithelial cells. Our results illustrate a novel mechanism of evolution that may contribute to the complexity of Src kinase regulation.

Brignatz, C., Paronetto, M., Opi, S., Cappellari, M., Audebert, S., Feuillet, V., et al. (2009). Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn. MOLECULAR AND CELLULAR BIOLOGY, 29(24), 6438-48 [10.1128/MCB.00398-09].

Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn

SETTE, CLAUDIO;
2009

Abstract

Src family kinases are central regulators of a large number of signaling pathways. To adapt to the idiosyncrasies of different cell types, these kinases may need a fine-tuning of their intrinsic molecular control mechanisms. Here, we describe on a molecular level how the Fyn kinase uses alternative splicing to adapt to different cellular environments. Using structural analysis, site-directed mutagenesis, and functional analysis, we show how the inclusion of either exon 7A or 7B affects the autoinhibition of Fyn and how this changes the SH3-dependent interaction and tyrosine phosphorylation of Sam68, with functional consequences for the Sam68-regulated survival of epithelial cells. Our results illustrate a novel mechanism of evolution that may contribute to the complexity of Src kinase regulation.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16
English
Con Impact Factor ISI
Proto-Oncogene Proteins c-fyn; bcl-X Protein; Evolution, Molecular; Isoenzymes; Cell Line; src Homology Domains; Animals; DNA-Binding Proteins; Alternative Splicing; Humans; Apoptosis; Adaptor Proteins, Signal Transducing; Signal Transduction; Recombinant Fusion Proteins; Mutagenesis, Site-Directed; Molecular Sequence Data; Tissue Distribution; Sequence Alignment; RNA-Binding Proteins; Amino Acid Sequence; Exons
Brignatz, C., Paronetto, M., Opi, S., Cappellari, M., Audebert, S., Feuillet, V., et al. (2009). Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn. MOLECULAR AND CELLULAR BIOLOGY, 29(24), 6438-48 [10.1128/MCB.00398-09].
Brignatz, C; Paronetto, M; Opi, S; Cappellari, M; Audebert, S; Feuillet, V; Bismuth, G; Roche, S; Arold, S; Sette, C; Collette, Y
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/30493
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 21
social impact