The Drosophila melanogaster ribosomal S6 kinase II-encoding sequence

doi:10.1016/0378-1119(94)90396-4

Gene

Volume 144, Issue 2, 8 July 1994, Pages 309-310

https://doi.org/10.1016/0378-1119(94)90396-4 Get rights and content

Abstract

A cDNA encoding the Drosophila melanogaster p90 ribosomal S6 kinase II (RSK) was isolated from an eye-antennal imaginal disc library and sequenced. The conceptually translated protein is 60–63% identical to vertebrate RSK homologs and contains a perfectly conserved mitogen-activated protein kinase phosphorylation site. The gene was mapped to the base of the X chromosome in division 20 by in situ hybridization to polytene chromosomes.

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Cited by (21)

Modelling Learning and Memory in Drosophila to Understand Intellectual Disabilities
2020, Neuroscience
Citation Excerpt :
Gene transcription controlled by CREB represents an important molecular switch, controlling the transition from short-term, protein synthesis-independent memory formation to long-term, protein synthesis-dependent memory storage (DeZazzo and Tully, 1995; Martin et al., 1997; Alberini, 2009). In Drosophila, there is only one RSK gene, demonstrating the greatest homology with the human RSK2 gene (60–63% sequence identity at protein level) (Wassarman et al., 1994 and Table 1.). Interestingly, in Drosophila, RSK negatively regulates spine morphology in synaptic boutons by inhibition of ERK signaling (Fischer et al., 2009) and its full deletion leads to defects in learning (Putz et al., 2004; Neuser et al., 2008), indicating that its function in the brain is conserved across species.
Neurodevelopmental disorders (NDDs) include a large number of conditions such as Fragile  X  syndrome, autism spectrum disorders and Down syndrome, among others. They are characterized by limitations in adaptive and social behaviors, as well as intellectual disability (ID). Whole-exome and whole-genome sequencing studies have highlighted a large number of NDD/ID risk genes. To dissect the genetic causes and underlying biological pathways, in vivo experimental validation of the effects of these mutations is needed. The fruit fly, Drosophila melanogaster, is an ideal model to study NDDs, with highly tractable genetics, combined with simple behavioral and circuit assays, permitting rapid medium-throughput screening of NDD/ID risk genes. Here, we review studies where the use of well-established assays to study mechanisms of learning and memory in Drosophila has permitted insights into molecular mechanisms underlying IDs. We discuss how technologies in the fly model, combined with a high degree of molecular and physiological conservation between flies and mammals, highlight the Drosophila system as an ideal model to study neurodevelopmental disorders, from genetics to behavior.
The C-terminal kinase and ERK-binding domains of Drosophila S6KII (RSK) are required for phosphorylation of the protein and modulation of circadian behavior
2012, Journal of Biological Chemistry
Citation Excerpt :
N-terminal kinase activity was thought to be essential for RSK function until a recent study demonstrated an alternative role for RSK in fly eye development as a non-catalytic, scaffolding protein (15). The mammalian genome encodes four isoforms of RSK (RSK 1–4) while only a single isoform has been described for Drosophila melanogaster (dRSK or S6KII) that has ∼60% amino acid identity with RSK1 (16). Whereas there have been extensive studies of RSK structure and function using mammalian cell-based assays, detailed studies of fly S6KII functional domains have not been reported even though the kinase is known to be important for memory functions and circadian behavior (17–19).
A detailed structure/function analysis of Drosophila p90 ribosomal S6 kinase (S6KII) or its mammalian homolog RSK has not been performed in the context of neuronal plasticity or behavior. We previously reported that S6KII is required for normal circadian periodicity. Here we report a site-directed mutagenesis of S6KII and analysis of mutants, in vivo, that identifies functional domains and phosphorylation sites critical for the regulation of circadian period. We demonstrate, for the first time, a role for the S6KII C-terminal kinase that is independent of its known role in activation of the N-terminal kinase. Both S6KII C-terminal kinase activity and its ERK-binding domain are required for wild-type circadian period and normal phosphorylation status of the protein. In contrast, the N-terminal kinase of S6KII is dispensable for modulation of circadian period and normal phosphorylation of the protein. We also show that particular sites of S6KII phosphorylation, Ser-515 and Thr-732, are essential for normal circadian behavior. Surprisingly, the phosphorylation of S6KII residues, in vivo, does not follow a strict sequential pattern, as implied by certain cell-based studies of mammalian RSK protein.
P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons
2009, Molecular and Cellular Neuroscience
Mutations in Ribosomal s6 kinase 2 (Rsk2) are associated with severe neuronal dysfunction in Coffin–Lowry syndrome (CLS) patients, flies and mice. So far, the mechanisms of how Rsk2 regulates development, maintenance and activity of neurons are not understood. We have investigated the consequences of Rsk2 deficiency in mouse spinal motoneurons. Survival of isolated Rsk2 deficient motoneurons is not reduced, but these cells grow significantly longer neurites. Conversely, overexpression of a constitutively active form of Rsk2 leads to reduced axon growth. Increased axon growth in Rsk2 deficient neurons was accompanied by higher Erk 1/2 phosphorylation, and the knockout phenotype could be rescued by pharmacological inhibition of MAPK/Erk kinase (Mek). These data indicate that Rsk2 negatively regulates axon elongation via the MAPK pathway. Thus, the functional defects observed in the nervous system of CLS patients and animal models with Rsk2 deficiency might be caused by dysregulated neurite growth rather than primary neurodegeneration.
Involvement of p90 ribosomal S6 kinase in termination of cell cycle arrest during development of Artemia-encysted embryos
2008, Journal of Biological Chemistry
Artemia has evolved a unique developmental pattern of encysted embryos to cope with various environmental threats. Cell divisions totally cease during the preemergence developmental stage from gastrula to prenauplius. The molecular mechanism of this, however, remains unknown. Our study focuses on the involvement of p90 ribosomal S6 kinase (RSK), a family of serine/threonine kinase-mediating signal transduction downstream of mitogen-activated protein kinase cascades, in the termination of cell cycle arrest during the post-embryonic development of Artemia-encysted gastrula. With immunochemistry, morphology, and cell cycle analysis, the identified Artemia RSK was established to be specifically activated during the post-embryonic and early larval developmental stages when arrested cells of encysted embryos resumed mitoses. In vivo knockdown of RSK activity by RNA interference, kinase inhibition, and antibody neutralization consistently induced defective larvae with distinct gaps between the exoskeleton and internal tissues. In these abnormal individuals, mitoses were detected to be largely inhibited in the affected regions. These results display the requirement of RSK activity during Artemia development and suggest its role in termination of cell cycle (G₂/M phase) arrest and promotion of mitogenesis. Our findings may, thus, provide insights into the regulation of cell division during Artemia post-embryonic development and reveal further aspects of RSK functions.
Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila
2004, Cell
Multicellular organisms must integrate growth and differentiation precisely to pattern complex tissues. Despite great progress in understanding how different cell fates are induced, it is poorly understood how differentiation decisions are temporally regulated. In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway. We find that loss of tsc1 disrupts patterning due to a loss of temporal control of differentiation. tsc1 controls the timing of differentiation downstream or in parallel to the RAS/MAPK pathway. Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious differentiation while decreased signaling leads to delays in differentiation. Importantly, cell fates are unchanged, but tissue organization is lost upon loss of developmental timing controls. These data suggest that intricate developmental decisions are coordinated with nutritional status and tissue growth by the InR signaling pathway.
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
1999, Molecular and Cellular Endocrinology
Extracellular signals activate mitogen-activated protein kinase (MAPK) cascades to execute complex cellular programs, like proliferation, differentiation and apoptosis. In mammalian cells, three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), which is activated by growth factors, peptide hormones and neurotransmitters, and Jun kinase (JNK) and p38 MAPK, which are activated by cellular stress stimulus as well as growth factors. This review describes the family of 90 kDa ribosomal S6 kinases (RSK; also known as p90^rsk or MAPK-activated protein kinase-1, MAPKAP-K1), which were among the first substrates of ERK to be discovered and which has proven to be a ubiquitous and versatile mediator of ERK signal transduction. RSK is composed of two functional kinase domains that are activated in a sequential manner by a series of phosphorylations. Recently, a family of RSK-related kinases that are activated by ERK as well as p38 MAPK were discovered and named mitogen- and stress-activated protein kinases (MSK). A number of cellular functions of RSK have been proposed. (1) Regulation of gene expression via association and phosphorylation of transcriptional regulators including c-Fos, estrogen receptor, NFκB/IκBα, cAMP-response element-binding protein (CREB) and CREB-binding protein; (2) RSK is implicated in cell cycle regulation in Xenopus laevis oocytes by inactivation of the Myt1 protein kinase leading to activation of the cyclin-dependent kinase p34^cdc2; (3) RSK may regulate protein synthesis by phosphorylation of polyribosomal proteins and glycogen synthase kinase-3; and (4) RSK phosphorylates the Ras GTP/GDP-exchange factor, Sos leading to feedback inhibition of the Ras-ERK pathway.

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^☆: On request, the authors will supply detailed experimental evidence for the conclusions presented in this Brief Note.

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Abstract

References (9)

Basal local alignment search tool

J. Mol. Biol.

Structure, expression and regulation of protein kinases involved in the phosphorylation of ribosomal protein S6

J. Biol. Chem.

opa: A novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in D. melanogaster

Cell

Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase

Mol. Cell. Biol.

Cited by (21)

Modelling Learning and Memory in Drosophila to Understand Intellectual Disabilities

The C-terminal kinase and ERK-binding domains of Drosophila S6KII (RSK) are required for phosphorylation of the protein and modulation of circadian behavior

P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons

Involvement of p90 ribosomal S6 kinase in termination of cell cycle arrest during development of Artemia-encysted embryos

Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila

Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction

Brief noteThe Drosophila melanogaster ribosomal S6 kinase II-encoding sequence☆

Abstract

J. Mol. Biol.

J. Biol. Chem.

Cell

Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase

Mol. Cell. Biol.

Brief note
The Drosophila melanogaster ribosomal S6 kinase II-encoding sequence☆