Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development.
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.
Kim
Myungjin
M
Department of Biological Sciences, National Creative Research Initiatives Center for Cell Growth Regulation, Korea Advanced Institute of Science and Technology, Yusong, Taejon, Korea.
Lee
Jun Hee
JH
Koh
Hyongjong
H
Lee
Soo Young
SY
Jang
Cholsoon
C
Chung
Cecilia J
CJ
Sung
Jung Hwan
JH
Blenis
John
J
Chung
Jongkyeong
J
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D012160:Retina / Q000196:embryology / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014921:Wings, Animal / Q000098:blood supply / Q000196:embryology / Q000502:physiology
D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases