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http://purl.uniprot.org/citations/11237865http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11237865http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11237865http://www.w3.org/2000/01/rdf-schema#comment"The transcription factor, forkhead in rhabdomyosarcoma (FKHR), is phosphorylated at three amino acid residues (Thr-24, Ser-256 and Ser-319) by protein kinase B (PKB)alpha. In the present study, mutagenesis has been used to study the roles of these phosphorylation events in regulating FKHR function in transfected HEK-293 cells. We find that the overexpression of FKHR[S256A] (where Ser-256-->Ala) blocks PKB activity in cells, preventing phosphorylation of the endogenous substrates FKHRL1 and glycogen synthase kinase-3. Thus some reported effects of overexpression of this and other mutants may be indirect, and result from suppression of the phosphorylation of other sites on FKHR and/or other PKB substrates. For example, we have shown that Thr-24 phosphorylation alone is critical for interaction with 14-3-3 proteins, and that the substitution of Ser-256 with an alanine residue indirectly blocks 14-3-3 protein binding by preventing the phosphorylation of Thr-24. We also found that insulin-like growth factor (IGF)-1 and serum-induced nuclear exclusion of FKHR[S256A] depends on the degree of overexpression of this mutant. Our results indicated that the interaction of FKHR with 14-3-3 proteins was not required for IGF-1-stimulated exclusion of FKHR from the nucleus. We present evidence in support of another mechanism, which depends on the phosphorylation of Ser-256 and may involve the masking of a nuclear localization signal. Finally, we have demonstrated that the failure of IGF-1 to suppress transactivation by FKHR[S256A] is not explained entirely by its failure to bind 14-3-3 proteins or to undergo nuclear exclusion. This result suggests that Ser-256 phosphorylation may also suppress transactivation by FKHR by yet another mechanism, perhaps by disrupting the interaction of FKHR with target DNA binding sites and/or the function of the transactivation domain."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.org/dc/terms/identifier"doi:10.1042/0264-6021:3540605"xsd:string
http://purl.uniprot.org/citations/11237865http://purl.org/dc/terms/identifier"doi:10.1042/0264-6021:3540605"xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Guo S."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Guo S."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Cohen P."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Cohen P."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Prescott A.R."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Prescott A.R."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Rena G."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Rena G."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Unterman T.G."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/author"Unterman T.G."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/name"Biochem. J."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/name"Biochem. J."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/pages"605-612"xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/pages"605-612"xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/title"Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/title"Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting."xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/volume"354"xsd:string
http://purl.uniprot.org/citations/11237865http://purl.uniprot.org/core/volume"354"xsd:string
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