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A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation.

ABSTRACT: The dynamic regulation of ERK1 and -2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. These studies identify RasGRP2 as a novel substrate of ERK1/2 and define a negative-feedback loop that regulates the BRaf-MEK-ERK signaling cascade. This negative-feedback loop determines the amplitude and duration of active ERK1/2.

SUBMITTER: Ren J

PROVIDER: S-EPMC4872870 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation.

Ren Jinqi J Cook Aaron A AA Bergmeier Wolfgang W Sondek John J

Biochemical and biophysical research communications 20160421 1

The dynamic regulation of ERK1 and -2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates Ras ...[more]

PMID: 27107697

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