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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#_4 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#_3 http://www.w3.org/ns/prov#value The phosphorylation of a previously uncharacterized protein of apparent M(r) approximately 140,000 was found to be increased when rat adipocytes were incubated with insulin. The sequences of peptides generated by digesting the protein with trypsin matched perfectly with sequences in mouse lipin. Lipin is the product of the gene that is mutated in fatty liver dystrophy (fld) mice [Peterfy, M., Phan, J., Xu, P. & Reue, K (2001) Nat. Genet. 27, 121-124], which exhibit several phenotypic abnormalities including hyperlipidemia, defects in adipocyte differentiation, impaired glucose tolerance, and slow growth. When immunoblots were prepared with lipin antibodies, both endogenous adipocyte lipin and recombinant lipin overexpressed in HEK293 cells appeared as bands ranging in apparent M(r) from 120,000 to 140,000. Incubating adipocytes with insulin decreased the electrophoretic mobility and stimulated the phosphorylation of both Ser and Thr residues in lipin. The effects of insulin were abolished by inhibitors of phosphatidylinositol 3-OH kinase, and by rapamycin, a specific inhibitor of the mammalian target of rapamcyin (mTOR). The inhibition by rapamycin was blocked by FK506, which competitively inhibits those effects of rapamycin that are mediated by inhibition of mTOR. Moreover, amino acids, which activate mTOR, mimicked insulin by increasing lipin phosphorylation in a rapamycin-sensitive manner. Thus, lipin represents a target of the mTOR pathway, and potentially links this nutrient-sensing pathway to adipocyte development. http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11792863 http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11792863 http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#_3 http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8#pubinfo http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8 http://purl.org/dc/terms/created 2014-07-03T14:31:46.168+02:00 http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAP9Afw9DTDng_6tpSRIrOv3rtmvP02k1UdpeKIKfShW8 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234