PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk.
Mol Syst Biol
; 5: 246, 2009.
Article
em En
| MEDLINE
| ID: mdl-19225459
ABSTRACT
Although it is appreciated that canonical signal-transduction pathways represent dominant modes of regulation embedded in larger interaction networks, relatively little has been done to quantify pathway cross-talk in such networks. Through quantitative measurements that systematically canvas an array of stimulation and molecular perturbation conditions, together with computational modeling and analysis, we have elucidated cross-talk mechanisms in the platelet-derived growth factor (PDGF) receptor signaling network, in which phosphoinositide 3-kinase (PI3K) and Ras/extracellular signal-regulated kinase (Erk) pathways are prominently activated. We show that, while PI3K signaling is insulated from cross-talk, PI3K enhances Erk activation at points both upstream and downstream of Ras. The magnitudes of these effects depend strongly on the stimulation conditions, subject to saturation effects in the respective pathways and negative feedback loops. Motivated by those dynamics, a kinetic model of the network was formulated and used to precisely quantify the relative contributions of PI3K-dependent and -independent modes of Ras/Erk activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas ras
/
Fosfatidilinositol 3-Quinases
/
Receptor Cross-Talk
/
MAP Quinases Reguladas por Sinal Extracelular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article