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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#_5 http://www.w3.org/ns/prov#value DOC-2/DAB2, a novel phosphoprotein with signal-transducing capability, inhibits human prostatic cancer cells (Tseng, C.-P., Ely, B. D., Li, Y., Pong, R.-C., and Hsieh, J.-T. (1998) Endocrinology 139, 3542-3553). However, its mechanism of action is not understood completely. This study delineates the functional significance of DOC-2/DAB2 protein phosphorylation and demonstrates that in vivo activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) induces DOC-2/DAB2 phosphorylation, including a serine residue at position 24. Mutation of Ser(24) to Ala reduced DOC-2/DAB2 phosphorylation by PKC. Using a synthetic Ser(24) peptide (APS(24)KKEKKKGSEKTD) or recombinant DOC-2/DAB2 as substrates, PKCbetaII, PKCgamma, and PKCdelta (but not casein kinase II) directly phosphorylated Ser(24) in vitro. This indicates that DOC-2/DAB2 is a PKC-specific substrate. Since expression of wild-type DOC-2/DAB2, but not the S24A mutant, inhibited TPA-induced AP-1 activity in prostatic epithelial cells, phosphorylation of Ser(24) appears to play a critical role in modulating TPA-induced AP-1 activity. Taken together, these data suggest that PKC-regulated phosphorylation of DOC-2/DAB2 protein may help its growth inhibitory function. http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/10542228 http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/10542228 http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#_5 http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0#pubinfo http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0 http://purl.org/dc/terms/created 2014-07-03T14:29:49.021+02:00 http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAsRSuDegu5GrzLv_7wBHFn7gzCIaj-3SaOv1qptX2iK0 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234