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PMID:16763554

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Citation

Kim, M, Lee, JH, Koh, H, Lee, SY, Jang, C, Chung, CJ, Sung, JH, Blenis, J and Chung, J (2006) Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development. EMBO J. 25:3056-67

Abstract

Although p90 ribosomal S6 kinase (RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase (Ras/ERK) pathway, its endogenous role, and precise molecular function remain unclear. Using gain-of-function and null mutants of RSK, its physiological role was successfully characterized in Drosophila. Surprisingly, RSK-null mutants were viable, but exhibited developmental abnormalities related to an enhanced ERK-dependent cellular differentiation such as ectopic photoreceptor- and vein-cell formation. Conversely, overexpression of RSK dramatically suppressed the ERK-dependent differentiation, which was further augmented by mutations in the Ras/ERK pathway. Consistent with these physiological phenotypes, RSK negatively regulated ERK-mediated developmental processes and gene expressions by blocking the nuclear localization of ERK in a kinase activity-independent manner. In addition, we further demonstrated that the RSK-dependent inhibition of ERK nuclear migration is mediated by the physical association between ERK and RSK. Collectively, our study reveals a novel regulatory mechanism of the Ras/ERK pathway by RSK, which negatively regulates ERK activity by acting as a cytoplasmic anchor in Drosophila.

Links

PubMed PMC1500987 Online version:10.1038/sj.emboj.7601180

Keywords

Active Transport, Cell Nucleus; Amino Acid Sequence; Animals; Cell Differentiation; Cell Nucleus/metabolism; Drosophila/embryology; Drosophila/physiology; Embryo, Nonmammalian/physiology; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases/physiology; Female; Male; Molecular Sequence Data; Mutation; Phosphorylation; Protein Binding; Retina/embryology; Retina/physiology; Ribosomal Protein S6 Kinases, 90-kDa/genetics; Ribosomal Protein S6 Kinases, 90-kDa/physiology; Signal Transduction; Wing/blood supply; Wing/embryology; Wing/physiology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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