Disease relevance of RPS6KB2

• Immunohistochemical analysis of S6K1 and S6K2 expression in endometrial adenocarcinomas [1].
• FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2 [2].
• Immunohistochemical analysis of S6K1 and S6K2 expression in human breast tumors [3].
• To investigate the catalytic properties of the Brassica oleracea S-locus receptor kinase (SRK), we have expressed the domain that is homologous to protein kinases as a fusion protein in Escherichia coli [4].
• In the prediction of ametropia, the SRK method showed a tendency to predict refractions that were lower than the actual values in hyperopic eyes and higher than the actual values in myopic eyes [5].

Psychiatry related information on RPS6KB2

• No case in the standard SRK/T group and 6 cases (66.66%) in the double-K group achieved a +/-0.5 D SE [6].

High impact information on RPS6KB2

• In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl-X(L) and prosurvival effects [2].
• RNAi-mediated downregulation of B-Raf, PKCepsilon or S6K2 abolishes FGF-2-mediated survival [2].
• Thus, including SRK, the S locus in the S15 haplotype contains at least three members of the S gene family [7].
• Phosphorylation was shown to occur in trans, suggesting the existence of constitutive homooligomers of membrane-anchored recombinant SRK [8].
• To investigate the physiological relevance of these results, we have examined the oligomeric status of SRK in planta in cross-linking experiments and by velocity sedimentation on sucrose gradients [8].

Biological context of RPS6KB2

• The majority of the regulatory phosphorylation sites identified in p70alpha are conserved in p70beta [9].
• However, the amino acid sequence of p70beta differs from that of p70alpha in the noncatalytic amino-terminal region and in the carboxyl-terminal tail, which contains a proline-rich region [9].
• These results indicate that p70beta has the potential to participate in the regulation of protein synthesis and the cell cycle [9].
• Consistently, the nuclear export inhibitor leptomycin B inhibited S6K2 activation [10].
• Interestingly, genetic experiments predict that a substrate that is specific to S6K1 but not S6K2 regulates cell growth [11].

Anatomical context of RPS6KB2

• In contrast to S6K2, S6K1 was activated in both SCLC cell lines [12].
• RESULTS: In normal endometrial epithelial cells both S6K1 and S6K2 were expressed on the low level [1].
• For anterior chamber lenses, the SRK II formula was significantly less accurate than the other three formulas in eyes with long axial length [13].
• Genetic predisposition for KLS could be related to hyperexcitability and synchronization of interneurons within the perisylvian cortices, which generate the spike-waves [14].

Associations of RPS6KB2 with chemical compounds

• Ribosomal S6 kinase 2 (S6K2) is a recently identified serine/threonine protein kinase that phosphorylates the 40 S ribosomal protein S6 in vitro [15].
• Site-specific mutation of these sites to alanine completely desensitizes S6K2 to activating inputs, whereas mutation to aspartic acid to mimic phosphorylation results in an activated enzyme which is hypersensitive to activating inputs [15].
• However, unlike S6K1, changing Thr-388 to glutamic acid in S6K2 renders the kinase fully active [16].
• Quantitative mass spectrometry reveals that serine 383/385 phosphorylation is sensitive to RNA interference (RNAi)-mediated S6K1 reduction, but not S6K2 reduction [11].
• We demonstrate that similar to S6K1 the serum activation of S6K2 in cells is dependent on mTOR kinase activity, amino acid sufficiency, and phosphatidic acid [10].

Regulatory relationships of RPS6KB2

• We have recently demonstrated that S6K2 is regulated similarly to S6K1 by the mammalian target of rapamycin pathway and by multiple PI3-K pathway effectors in vivo [15].
• Pretreatment of cells with the mitogen-activated protein-extracellular signal-regulated kinase kinase (MEK) inhibitor U0126 inhibited S6K2 activation to a greater extent than S6K1 [15].
• Similar to S6K1, S6K2 is activated by mitogens and by constitutively active PI3K, and is inhibited by rapamycin as well as wortmannin [17].

Other interactions of RPS6KB2

• The C-terminal sequence of S6K2 is divergent from that of S6K1 [18].
• Similarly to p70alpha, the catalytic activity of p70beta toward ribosomal protein S6 could be rapidly activated by serum, insulin, and phorbol ester in transiently transfected cells [9].
• Two isoforms of p70beta, referred to as beta1 (495 amino acids) and beta2 (482 amino acids), could be expressed from the single gene either by alternative mRNA splicing or by the use of alternative start codons [9].
• Thus, MEK-dependent inputs to C-terminal phosphorylation sites appear to be essential for relief of S6K2 inhibition but less critical for activation of S6K1 [15].
• We demonstrate that the inhibitory effects of the S6K2 C-terminal domain are only partly attributable to the nuclear localization signal but that three C-terminal proline-directed potential mitogen-activated protein kinase phosphorylation sites are critical mediators of this inhibitory effect [15].

Analytical, diagnostic and therapeutic context of RPS6KB2

• Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region [9].
• Development of the SRK/T intraocular lens implant power calculation formula [19].
• RESULTS: The CTR and control groups were compared using SRK/T and Holladay 2 [20].
• CONCLUSION: Double-K modification of the SRK/T formula improved the accuracy of IOL power calculation after LASIK and PRK [6].
• RT-PCR was used to amplify three SRK-like cDNAs from stigmas of S(1)S(2) heterozygotes, but the expression patterns of these cDNAs suggest that they are unlikely to be directly involved in SI or pollen-stigma interactions in contrast to SSI in the Brassicaceae [21].

References