Research ResourceMAPK Signaling

Large-Scale Discovery of ERK2 Substrates Identifies ERK-Mediated Transcriptional Regulation by ETV3

Sci. Signal.  25 Oct 2011:
Vol. 4, Issue 196, pp. rs11
DOI: 10.1126/scisignal.2002010

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Discovering ERK2 Substrates

Extracellular signal–regulated kinase 2 (ERK2) is one of two closely related mitogen-activated protein kinases (MAPKs) that function downstream of many receptors. Because ERK2 and ERK1 are usually activated under the same conditions and are recognized by the same antibodies, it can be difficult to assign specific substrates and functions to these related proteins. Carlson et al. combined mass spectrometry analysis with chemical genetics to identify ERK2-specific substrates. Their work identified targets in diverse pathways suggesting mechanisms for crosstalk with MAPK signaling. Additionally, detailed analysis of the transcriptional repressor ETV3 suggested that phosphorylation by ERK2 on sites in both canonical and noncanonical motifs inhibited its DNA binding capacity, which may poise cells for a transient transcriptional burst in response to stimuli that activate ERK signaling or those that arrive concurrently.

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