High impact information on Rps6ka2

• Self-reactive B cells lacking the phosphatase CD45 did not exhibit calcium oscillations or ERK/pp90rsk activation, nor did they repond negatively to self-antigen [1].
• In naive cells, foreign antigen triggered a large biphasic calcium response and activated nuclear signals through NF-AT, NF-kappa B, JNK, and ERK/pp90rsk [1].
• Mitogen-activated Swiss mouse 3T3 RSK kinases I and II are related to pp44mpk from sea star oocytes and participate in the regulation of pp90rsk activity [2].
• The mouse Rsk3 gene was prominently expressed in the developing neural and sensory tissues, whereas Rsk1 gene expression was the strongest in various other tissues with high proliferative activity, suggesting distinct roles during development [3].
• Quantitative phosphorylation of pp90rsk continued to increase after its S6 kinase activity began its return towards basal levels [4].

Biological context of Rps6ka2

• The complete mouse Rsk3 gene is encoded in the region Leh66a of t-haplotypes and Leh66EI of the wild-type chromosome [5].
• In the search for genes in the genomic region Leh66EI, we have identified the mouse homolog of human ribosome S6 kinase 3 (RSK3) on cosmid DNA [5].
• Regulation of pp90rsk phosphorylation and S6 phosphotransferase activity in Swiss 3T3 cells by growth factor-, phorbol ester-, and cyclic AMP-mediated signal transduction [4].
• Here we examine alterations in pp90rsk phosphorylation and S6 phosphotransferase activity in response to regulators of multiple signal transduction systems: purified growth factors, phorbol ester, changes in cyclic AMP (cAMP) levels, and sodium vanadate [4].
• All reagents tested increased pp90rsk serine and threonine phosphorylation, but only those agents that regulate cell proliferation and sodium vanadate activated its S6 kinase activity [4].

Anatomical context of Rps6ka2

• Rsk3 is expressed in embryos and in several adult organs including testis [5].
• These results provide compelling evidence that in fibroblasts and PC12 cells ERK1 plays a direct role in the phosphorylation of pp90rsk and that pp90rsk represents a physiologically relevant substrate of extracellular-regulated kinases [6].
• Rapamycin completely blocked activation of pp70-S6 kinase by insulin in 3T3-L1 adipocytes, but did not inhibit insulin-stimulated glucose transport, translocation of GLUT4 to the cell surface, or activation of pp90rsk or pp44mapk by insulin [7].
• Based upon these data a signal linkage map for activation of glycogen synthase in vivo in skeletal muscle can be constructed in which JNK mediates activation of glycogen synthase via RSK3 [8].
• Activation of MAP kinases, pp90rsk and pp70-S6 kinases in mouse mast cells by signaling through the c-kit receptor tyrosine kinase or Fc epsilon RI: rapamycin inhibits activation of pp70-S6 kinase and proliferation in mouse mast cells [9].

Associations of Rps6ka2 with chemical compounds

• With this assay we have ientified a pp60v-src-, growth factor-, phorbol ester-, and vanadate-regulated serine/threonine protein kinase activity that is not related to two other cofactor-independent, growth-regulated protein kinases, pp70-S6 protein kinase and pp90rsk [10].
• The pp90rsk phosphothreonine content paralleled the ERK1 activity more closely than the phosphoserine level [6].
• In addition, our data also show that preincubation of cells with a tyrosine kinase inhibitor herbimycin A, but not with a serine/threonine kinase inhibitor H7, blocks activation of mitogen-activated protein kinases and pp90rsk [11].
• Interestingly, H7, but not herbimycin A, inhibits pp90rsk activity in the in vitro kinase assays [11].

Regulatory relationships of Rps6ka2

• However, epidermal growth factor and fetal bovine serum were equipotent with insulin in stimulating pp90rsk and pp44mapk activities in adipocytes, but were without effect on hexose uptake [12].
• We have demonstrated that Jak tyrosine kinases, MAP kinases and pp90rsk are highly activated by IL-11 and related cytokines [13].

Other interactions of Rps6ka2

• The mouse Rsk3 gene maps to the Leh66 elements carrying the t-complex responder Tcr [5].
• A detailed examination of the mitogen-regulated activation kinetics of rsk-kinase and pp90rsk activities demonstrated that they are coordinately regulated [10].
• We report here that mouse mast cells stimulated either with SCF or with IgE and specific antigen exhibit a remarkably similar pattern of activation of mitogen-activated protein kinases (MAPK), 90 kDa-S6 kinases (pp90rsk), and pp70-S6 kinases (pp70-S6K) [9].
• In addition, we have identified pp90rsk as one of the H7 sensitive protein kinases critical for primary response gene expression induced by IL-11 [13].
• The metabolic and mitogenic actions of insulin have been proposed to be mediated by cellular serine/threonine kinases such as the ribosomal protein S6 kinases pp70-S6 (pp70-S6 kinase) and pp90rsk and the erk-encoded mitogen-activated protein kinases (pp42mapk and pp44mapk) [7].

Analytical, diagnostic and therapeutic context of Rps6ka2

• Western-blot analysis and immunocomplex kinase assays showed that wortmannin and demethoxyviridin specifically block the phosphorylation and activation of p70 S6 kinase without affecting the M(r) 90,000 ribosomal S6 kinase (p90rsk) or mitogen-activated protein kinases [14].

References