Disease relevance of Rps6ka1

• To confirm the role of p90RSK in cTnI phosphorylation in vivo, we generated adenovirus containing a dominant negative form of p90RSK (Ad-DN-p90RSK) [1].
• Apoptosis induced by 12 hours of anoxia followed by 24 hours' reoxygenation was significantly reduced in cells expressing Ad.DN-RSK (18.6+/-2.0%) compared with Ad.LacZ (29.3+/-5.4%) [2].
• Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning [3].
• Evidence of coordinate regulation of virulence in Salmonella typhimurium involving the rsk element of the 95-kilobase plasmid [4].

High impact information on Rps6ka1

• MAP kinases may participate in protein kinase cascades that link Src family protein-tyrosyl kinases to seryl-threonyl kinases such as those encoded by rsk and raf, which are putative substrates of MAP kinases [5].
• Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases [6].
• The responder gene has been identified as a fusion gene formed from a sperm motility kinase and a ribosomal S6 kinase [7].
• The S6K and RSK proteins are members of the AGC protein kinase family, and require PDK1 phosphorylation for activation [8].
• The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics [8].

Biological context of Rps6ka1

• However, in contrast to S6K, RSK and SGK, hydrophobic motif phosphorylation of these enzymes is not thought to control their activation by PDK1 [9].
• The expression of cyclin B1 and the phosphorylation of MAPK/p90rsk could still be detected in ALLN or MG-132-treated oocytes even at 8 h after parthenogenetic activation or insemination, which may account for the inhibition of PB2 emission and pronuclear formation [10].
• The injection of constitutively active mutant forms of Rsk1 and Rsk2 does not induce a cell cycle arrest in two-cell mouse embryos [11].
• We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK [12].
• Interestingly, however, the expression of transfected raf oncogenes did not induce MAPK or RSK activation, and the insulin-induced activation of these kinases was not blocked by expression of transfected dominant negative raf mutants [13].

Anatomical context of Rps6ka1

• Light- and clock-dependent regulation of ribosomal S6 kinase activity in the suprachiasmatic nucleus [14].
• MEK, ERK, and p90RSK are present on mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit [15].
• Under basal conditions, RSK1 is located in the cytosol and upon stimulation, RSK1 translocates to the plasma membrane where it is fully activated [16].
• After 5 min of serum stimulation, a portion of 14-3-3beta and RSK1 translocated to the membrane fraction, and immunofluorescence studies demonstrated colocalization of RSK1 and 14-3-3beta at the plasma membrane in vivo [16].
• Skeletal muscles from mice stimulated with insulin in vivo were used to evaluate relationships between the insulin receptor tyrosine kinase, mitogen-activated protein (MAP) kinase, p90rsk, p70 S6 kinase (p70S6k), and glycogen synthase [17].

Associations of Rps6ka1 with chemical compounds

• The ability of urea to activate the ERK effector and pivotal regulatory kinase, ribosomal S6 kinase (RSK), was investigated in mIMCD3 renal inner medullary collecting duct cells [18].
• p90 ribosomal S6 kinase 1 (RSK1) is a serine/threonine kinase that is activated by extracellular signal-related kinases 1/2 and phosphoinositide-dependent protein kinase 1 upon mitogen stimulation [16].
• Increased histone acetyltransferase and lysine acetyltransferase activity and biphasic activation of the ERK/RSK cascade in insular cortex during novel taste learning [19].
• Valproate time and concentration dependently increased activated phospho-ERK44/42 and phospho-RSK1 (ribosomal S6 kinase 1) levels in cultured cortical cells [20].
• Isoflurane decreased phosphorylation of the pro-apoptotic cofactors Bad and p90RSK and increased Akt phosphorylation [21].

Enzymatic interactions of Rps6ka1

• Finally, RANTES treatment induces nuclear translocation of phosphorylated RSK in astrocytes [22].
• In vitro, both RSK kinases and MBP kinase phosphorylated recombinant RSK and generated nearly identical two-dimensional tryptic phosphopeptide maps [23].
• We also found that p90 RSK directly phosphorylates CREB on Ser-133 following BCR cross-linking and is positioned downstream of nPKCdelta [24].

Regulatory relationships of Rps6ka1

• In vitro studies showed that GSK-3 was inactivated by 50% upon incubation with RSK purified from epidermal growth factor (EGF)-stimulated NIH/3T3 cells [25].
• We have previously shown that, in HCD-57 cells, erythropoietin (EPO) induces a biphasic activation of the ribosomal S6 kinase p70S6k, an enzyme playing a key role in the regulation of cell cycle progression [26].

Other interactions of Rps6ka1

• These findings provide genetic evidence that the phosphate groove of PDK1 is required for maximal activation of isoforms of S6K, SGK and RSK, but not PKC [9].
• Urea activates ribosomal S6 kinase (RSK) in a MEK-dependent fashion in renal mIMCD3 cells [18].
• Ribosomal S6 kinase p90rsk and mRNA cap-binding protein eIF4E phosphorylations correlate with MAP kinase activation during meiotic reinitiation of mouse oocytes [27].
• Kinases downstream of MAPK such as p90rsk and glycogen synthase kinase 3beta were only marginally affected [28].
• However, with the exception of c-Jun, transcription factors (Elk-1, GSK-3, Forkhead, p90RSK) decreased or remained unchanged [21].

Analytical, diagnostic and therapeutic context of Rps6ka1

• Using the yeast two-hybrid assay, we have identified ribosomal S6 kinase (RSK) to be a protein that associates with the cytoplasmic domain of the KGFR [29].
• Immunohistochemical and Western analysis were used to show that photic stimulation during the early and late night triggered the phosphorylation of RSK-1 at two sites that are targeted by ERK [14].
• Both stimuli induced the nuclear translocation of cytosolic RSK, as determined via immunofluorescence [18].
• Western blot analysis and immunocomplex kinase assays showed that these compounds inhibit the phosphorylation and activation of p70S6k without affecting the erk-encoded mitogen-activated protein (MAP) kinases or the rsk-encoded S6 kinase (p90rsk) [30].
• These in vivo data show that, in contrast to cell culture systems, cortical synaptic activity controls CRE-mediated gene expression without affecting CREB phosphorylation, possibly by modification of RSK and CREB-associated coregulators [31].

References