Skip Navigation

Publication Detail

Title: A two-dimensional ERK-AKT signaling code for an NGF-triggered cell-fate decision.

Authors: Chen, Jia-Yun; Lin, Jia-Ren; Cimprich, Karlene A; Meyer, Tobias

Published In Mol Cell, (2012 Jan 27)

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.

PubMed ID: 22206868 Exiting the NIEHS site

MeSH Terms: Animals; Cell Differentiation/drug effects*; Cell Differentiation/genetics; Cell Differentiation/physiology; Cell Proliferation/drug effects*; Cyclin D/genetics; Cyclin D/metabolism; Cyclin D/physiology; Extracellular Signal-Regulated MAP Kinases/metabolism*; Gene Expression Regulation; Gene Knockdown Techniques; MAP Kinase Signaling System*; Nerve Growth Factor/pharmacology*; PC12 Cells; Phosphatidylinositol 3-Kinases/metabolism; Phosphatidylinositol 3-Kinases/physiology; Protein Stability; Proto-Oncogene Proteins c-akt/metabolism*; Proto-Oncogene Proteins c-akt/physiology; Rats; ras GTPase-Activating Proteins/metabolism; ras GTPase-Activating Proteins/physiology

Back
to Top