Disease relevance of Pulsar

• Signaling mediated by the mammalian target of rapamycin kinase (mTOR) is activated during human cytomegalovirus (HCMV) infection. mTOR is found in two complexes differing by the binding partner, rictor or raptor [1].
• However, the efficacy of mTOR inhibitors alone in the treatment of patients with malignant gliomas is only modest, potentially because these agents rather than acting as mTOR kinase inhibitors instead interfere with the function of only mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not perturb all mTOR functions [2].
• Two peaks of association here contain the psoriasis candidate genes SLC9A3R (solute carrier family 9, isoform 3 regulatory factor), NAT9 (N-acetyltransferase superfamily), and RAPTOR (rapamycin (TOR)) [3].
• Hypersensitivity pneumonitis in a raptor handler and a wild bird fancier [4].
• Serologic evidence of West Nile virus infection in three wild raptor populations [5].

High impact information on Pulsar

• Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and phosphorylation of S6K1 at its hydrophobic motif [6].
• The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats) [7].
• Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression [8].
• Partial inhibition of raptor expression by RNA interference (RNAi) reduces mTOR-catalyzed 4EBP1 phosphorylation in vitro [9].
• mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery [8].

Biological context of Pulsar

• Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo [9].
• We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels [8].
• RNAi of C. elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR [9].
• Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha [9].
• These data suggest that, during HCMV infection, the rictor- and raptor-containing complexes are modified such that their substrate specificities and rapamycin sensitivities are altered [1].

Anatomical context of Pulsar

• Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton [10].
• DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species [11].
• Sperm viability at osmolalities >/=800 mOsm was higher (P: < 0.05) in raptor than poultry semen [12].
• The expression of the 4E-BP1 mutants replacing the TOS motif and phosphorylation sites, that are poor substrates for mTOR and have no or little dissociation ability from raptor and eIF4E, respectively, significantly reduced the size of K562 cells [13].
• Improved fluoroimmunoassays using the dye Alexa Fluor 647 with the RAPTOR, a fiber optic biosensor [14].

Associations of Pulsar with other chemical compounds

• The removal of extracellular amino acids or leucine alone inhibits the ability of the mammalian target of rapamycin (mTOR) to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP [15].
• Caffeine, wortmannin, LY294002, and rapamycin-FKBP12 also markedly inhibited mTOR activity in vitro, but unlike FTS, none of the other mTOR inhibitors appreciably changed the amount of raptor associated with mTOR [16].
• Imi1 conferred resistance to the imidazolinone herbicide imazamox, as shown by the in vitro assay for acetohydroxyacid synthase (AHAS) activity [17].
• The RAPTOR performs sandwich fluoroimmunoassays on the surface of small polystyrene optical waveguides for analyte detection [14].
• In this study, two raptor species, the common buzzard (Buteo buteo) and the little owl (Athene noctua), were investigated for lead and cadmium concentrations, using liver, kidneys, pectoral muscle, sternum bone, and feathers [18].

Gene context of Pulsar

• Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639 [19].
• Other recent work has shown that the protein raptor binds to mTOR and 4E-BP1 [20].
• In contrast, we find that Kog1, the yeast homologue of the mammalian Tor regulatory protein Raptor, interacts preferentially with Tor1p [21].
• Candidates for mediating the action of leucine to stimulate signaling through the mTOR pathway include TSC2, Rheb, and raptor [22].
• RESULTS: AtRaptor1B, a plant Raptor homologue, binds the AML1 (Arabidopsis Mei2-like 1) protein in a yeast two-hybrid assay [23].
• Our findings indicate that mTOR-mediated raptor phosphorylation plays an important role on activation of mTORC1 [24].

Analytical, diagnostic and therapeutic context of Pulsar

• Using state-of-the-art sequence analysis and structure-prediction methods a caspase-like domain in the N-terminal region of raptor proteins has been identified [25].
• Results of experiments involving size exclusion chromatography and coimmunoprecipitation of epitope-tagged subunits provide evidence that the major insulin-responsive form is dimeric mTORC1, a structure containing two heterotrimers of mTOR, raptor, and mLST8 [26].
• Developed to perform rapid fluoroimmunoassays in the field, the RAPTOR was designed to test samples for up to four different target analytes simultaneously [27].
• The capabilities of the portable, automated fiber optic biosensor, RAPTOR, have recently been evaluated [27].
• Plasma concentrations of LH were measured by a specific radioimmunoassay and pulsatile LH secretion was analysed using the Pulsar algorithm [28].

References