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Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate.

Abstract：

:The mitogen-activated protein kinase (MAPK) network is a conserved signalling module that regulates cell fate by transducing a myriad of growth-factor signals. The ability of this network to coordinate and process a variety of inputs from different growth-factor receptors into specific biological responses is, however, still not understood. We investigated how the MAPK network brings about signal specificity in PC-12 cells, a model for neuronal differentiation. Reverse engineering by modular-response analysis uncovered topological differences in the MAPK core network dependent on whether cells were activated with epidermal or neuronal growth factor (EGF or NGF). On EGF stimulation, the network exhibited negative feedback only, whereas a positive feedback was apparent on NGF stimulation. The latter allows for bi-stable Erk activation dynamics, which were indeed observed. By rewiring these regulatory feedbacks, we were able to reverse the specific cell responses to EGF and NGF. These results show that growth factor context determines the topology of the MAPK signalling network and that the resulting dynamics govern cell fate.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Santos SD,Verveer PJ,Bastiaens PI

doi

10.1038/ncb1543

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

324-30

issue

3

eissn

1465-7392

issn

1476-4679

pii

ncb1543

journal_volume

9

pub_type

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