Autophosphorylation of tyrosine residues on the cytoplasmic tail of the epidermal growth factor receptor ( EGFR) upon ligand binding leads to recruitment of the Grb2/Sos complex to the activated receptor and to activation of the Ras pathway. The major aim of this study was to ascertain to which extent the EGFR module ( receptor, Grb2, hSos1) could work in a lower eukaryote, completely devoid of tyrosine kinase receptors but possessing hortologues to mammalian Ras proteins. We show that the EGFR module can be functionally linked to the Ras/cAMP pathway in a Saccharomyces cerevisiae cdc25(ts) strain, as monitored by several independent biological readouts, including drop of budding index, decrease of cAMP level and acquisition of thermotolerance. Autophosphorylation of the receptor is a necessary step for RTK-dependent activation of the yeast Ras pathway, since genetic and pharmacological downregulation of the EGFR catalytic activity abolish coupling with the Ras/cAMP pathway. Thus, our results newly indicate that a RTK-based signal transduction module can be functionally coupled to the yeast Ras/cAMP pathway and that our system can be a valuable tool for the screen of drugs inhibiting the kinase activity of the receptor.

Busti, S., Sacco, E., Martegani, E., Vanoni, M. (2008). Functional coupling of the mammalian EGF receptor to the Ras/cAMP pathway in the yeast Saccharomyces cerevisiae. CURRENT GENETICS, 53(3), 153-162 [10.1007/s00294-007-0173-7].

Functional coupling of the mammalian EGF receptor to the Ras/cAMP pathway in the yeast Saccharomyces cerevisiae

BUSTI, STEFANO;SACCO, ELENA;MARTEGANI, ENZO;VANONI, MARCO ERCOLE
2008

Abstract

Autophosphorylation of tyrosine residues on the cytoplasmic tail of the epidermal growth factor receptor ( EGFR) upon ligand binding leads to recruitment of the Grb2/Sos complex to the activated receptor and to activation of the Ras pathway. The major aim of this study was to ascertain to which extent the EGFR module ( receptor, Grb2, hSos1) could work in a lower eukaryote, completely devoid of tyrosine kinase receptors but possessing hortologues to mammalian Ras proteins. We show that the EGFR module can be functionally linked to the Ras/cAMP pathway in a Saccharomyces cerevisiae cdc25(ts) strain, as monitored by several independent biological readouts, including drop of budding index, decrease of cAMP level and acquisition of thermotolerance. Autophosphorylation of the receptor is a necessary step for RTK-dependent activation of the yeast Ras pathway, since genetic and pharmacological downregulation of the EGFR catalytic activity abolish coupling with the Ras/cAMP pathway. Thus, our results newly indicate that a RTK-based signal transduction module can be functionally coupled to the yeast Ras/cAMP pathway and that our system can be a valuable tool for the screen of drugs inhibiting the kinase activity of the receptor.
Articolo in rivista - Articolo scientifico
CDC25; pathway reconstruction; heterologous expression; RTK signaling; nutrient starvation
English
2008
53
3
153
162
none
Busti, S., Sacco, E., Martegani, E., Vanoni, M. (2008). Functional coupling of the mammalian EGF receptor to the Ras/cAMP pathway in the yeast Saccharomyces cerevisiae. CURRENT GENETICS, 53(3), 153-162 [10.1007/s00294-007-0173-7].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/12974
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