Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development |
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| Authors: | Kim Myungjin Lee Jun Hee Koh Hyongjong Lee Soo Young Jang Cholsoon Chung Cecilia J Sung Jung Hwan Blenis John Chung Jongkyeong |
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| Affiliation: | Department of Biological Sciences, National Creative Research Initiatives Center for Cell Growth Regulation, Korea Advanced Institute of Science and Technology, Yusong, Taejon, Korea. |
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| 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. |
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