Sustained Signaling

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Science  23 Aug 2002:
Vol. 297, Issue 5585, pp. 1241
DOI: 10.1126/science.297.5585.1241c

How can activation of the extracellular signal-regulated kinase (ERK) pathway result in opposite cellular responses such as proliferation or differentiation. Murphy et al. suggest that the duration of activation of immediate early gene products (for example, c-Fos) may be a critical factor in interpreting the signal. Phosphorylation of c-Fos at positions Ser374 and Ser362 stimulated the phosphorylation of other residues (Thr325 and Thr331) by ERK via a docking motif called DEF (amino acids F343TYP in c-Fos). The initial phosphorylation events also prolong the lifetime of c-Fos, thus allowing cells to distinguish between transient and sustained ERK activation. Phosphorylation of Thr325 correlated with the stimulation of cell proliferation in response to sustained ERK signaling, whereas mutation of Thr325 and Thr331 or the DEF domain blocked c-Fos signaling. — NG

Nature Cell Biol.4, 556 (2002).

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