A two-dimensional ERK-AKT signaling code for an NGF-triggered cell-fate decision.
Mol Cell
; 45(2): 196-209, 2012 Jan 27.
Article
em En
| MEDLINE
| ID: mdl-22206868
ABSTRACT
Growth factors activate Ras, PI3K, and other signaling pathways. It is not well understood how these signals are translated by individual cells into a decision to proliferate or differentiate. Here, using single-cell image analysis of nerve growth factor (NGF)-stimulated PC12 cells, we identified a two-dimensional phospho-ERK (pERK)-phospho-AKT (pAKT) response map with a curved boundary that separates differentiating from proliferating cells. The boundary position remained invariant when different stimuli were used or upstream signaling components perturbed. We further identified Rasa2 as a negative feedback regulator that links PI3K to Ras, placing the stochastically distributed pERK-pAKT signals close to the decision boundary. This allows for uniform NGF stimuli to create a subpopulation of cells that differentiates with each cycle of proliferation. Thus, by linking a complex signaling system to a simpler intermediate response map, cells gain unique integration and control capabilities to balance cell number expansion with differentiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Fator de Crescimento Neural
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Sistema de Sinalização das MAP Quinases
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MAP Quinases Reguladas por Sinal Extracelular
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Proliferação de Células
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Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos