Disease relevance of KIAA1303

• 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].
• Hypersensitivity pneumonitis in a raptor handler and a wild bird fancier [3].
• Raptor species at risk from lead poisoning, including some of high conservation value, are described, and future priorities for lead poisoning research and policy are suggested [4].
• The aim of this epidemiological study was to investigate the seroprevalence of FHV-1 and owl herpesvirus (Strigid herpesvirus-1; StHV-1) infection in the UK, using virus neutralization tests, and to evaluate the prevalence of herpesvirus infection in captive and wild raptor populations [5].

High impact information on KIAA1303

• Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and phosphorylation of S6K1 at its hydrophobic motif [6].
• mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery [7].
• 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 [7].
• We identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is disrupted by high salt concentrations [8].
• When bound to FKBP12, rapamycin interacts with and inhibits the kinase activity of a multiprotein complex composed of mTOR, mLST8, and raptor (mTORC1) [9].

Biological context of KIAA1303

• 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].
• Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639 [10].
• A point mutation of the TOS motif also eliminates all in vitro mTOR-catalyzed 4E-BP1 phosphorylation and abolishes the raptor-dependent component of mTOR-catalyzed p70S6k phosphorylation in vitro [11].
• BACKGROUND: The target of rapamycin (TOR), in complex with the proteins raptor and LST8 (TOR complex 1), phosphorylates the p70S6K and 4E-BP1 to promote mRNA translation [12].
• Downregulation of raptor or rictor by RNA interference (RNAi) decreased cell motility [13].

Anatomical context of KIAA1303

• 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 [14].
• 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 [15].
• Sperm viability at osmolalities >/=800 mOsm was higher (P: < 0.05) in raptor than poultry semen [16].
• Improved fluoroimmunoassays using the dye Alexa Fluor 647 with the RAPTOR, a fiber optic biosensor [17].

Associations of KIAA1303 with chemical compounds

• 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 [18].
• Our results demonstrate the importance of localized PA generation for the mitogen-induced activation of mTOR, which is achieved by a specific interaction between PLD2 and mTOR/raptor [19].
• 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 [20].
• Raptor species in the Americas are recovering since restrictions on the use of dichlorodiphenyltrichloroethane (DDT) and the implementation of conservation measures, in effect constituting a hemisphere-wide predator-reintroduction experiment, and profound effects on populations of their prey are to be expected [21].
• The underlying technology (software Quasar and Raptor, respectively) specifically allows for induced fit, solvation phenomena and entropic effects [22].

Physical interactions of KIAA1303

• PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals [19].
• TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function [23].
• Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage [24].

Regulatory relationships of KIAA1303

• Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression [7].

Other interactions of KIAA1303

• Here we investigated the stability of endogenous mTOR/raptor complex in response to rapamycin in vivo, and to the direct addition of a FKBP12/rapamycin complex in vitro [25].
• Analysis using the phosphorylation site mutants indicated that phosphorylation of the priming and subsequent sites of 4E-BP1 was required for dissociation from raptor as well as for the release of eIF4E [14].
• Candidates for mediating the action of leucine to stimulate signaling through the mTOR pathway include TSC2, Rheb, and raptor [26].
• Another study found an association with SNPs in the RAPTOR gene, but not with the RUNX1 binding site polymorphism [24].
• Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis [27].

Analytical, diagnostic and therapeutic context of KIAA1303

• 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 [28].
• 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 [29].
• The RAPTOR performs sandwich fluoroimmunoassays on the surface of small polystyrene optical waveguides for analyte detection [17].
• The performance of the fluorescent dye Alexa Fluor 647 (AF647) was explored as an alternative to Cy5 for immunoassays on the RAPTOR, a fiber optic biosensor [17].
• Epornitic of avian pox in a raptor rehabilitation center [30].

References