Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-Jun transcription factor contains a transactivation domain that belongs to the "acidic" type of transcription activator. To determine the secondary structure of the Jun activation domain, we synthesized a peptide corresponding to amino acids 61 to 98 of c-Jun. Jun N-terminal kinases are able to phosphorylate Ser-63 and Ser-73 in vivo, which dramatically increases the transactivation potential of Jun. As this phosphorylation event may influence the secondary structure, we synthesized a second peptide containing two phosphoserine groups instead of serine in positions 63 and 73. Secondary structure predictions did not show potential for the peptides to adopt any stable, dominating conformation. Both peptides were purified and analyzed by circular dichroism spectroscopy. The peptides appeared to be flexible and essentially unstructured in aqueous solution. At acidic pH, we observed a decrease in the negative ellipticity at 202 nm, suggesting that some ordered structure might be present under these conditions. alpha-Helical conformation, as a dominating secondary structure, was induced in the presence of trifluoroethanol, and there was no significant difference between the unphosphorylated and phosphorylated peptides.
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PMID:A c-Jun activation domain peptide and its corresponding phosphopeptide have potential to adopt alpha-helical conformation. 873 81

Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63, by acting through IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of IRS-1, activation of Ras cycle and phosphorylation of c-Jun in this cell line. Serum starved MG-63 cells were (1) IGF-I stimulated and lysates were immunoprecipitated with polyclonal IRS-1 antibody or (2) metabolically labeled with [32P]orthophosphoric acid and then cells were treated with IGF-I. Cell lysates were immunoprecipitated with p21Ras antibody (Y13-259) and bound nucleotides were analysed by thin-layer chromatography. We demonstrated tyrosine phosphorylation of IRS-1/2 immunoprecipitated from MG-63 cells stimulated with IGF-I. We also showed an increased level of GTP in p21Ras immunoprecipitates from IGF-I treated cells. Nuclear extracts prepared from 32P-labeled cells before and after addition of IGF-I were immunoprecipitated with c-Jun antibody. After electrophoresis and autoradiography, phosphorylation of the c-Jun band was seen to be IGF-I independent. Phosphoamino acid analysis of the c-Jun band showed that phosphoserine was the major species.
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PMID:Insulin-like growth factor I activates insulin receptor substrate 1 and Ras in human osteosarcoma cells. 1045 87

Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the Toll/interleukin-1 (IL-1) receptor family by interacting with IL-1 receptor-associated kinase-1 (IRAK-1) after IRAK-1 is released from the receptor-MyD88 complex upon IL-1 stimulation. However, the molecular mechanisms underlying regulation of the IRAK-1/TRAF6 interaction are largely unknown. We have identified TIFA, a TRAF-interacting protein with a forkhead-associated (FHA) domain. The FHA domain is a motif known to bind directly to phosphothreonine and phosphoserine. In transient transfection assays, TIFA activates NFkappaBeta and c-Jun amino-terminal kinase. However, TIFA carrying a mutation that abolishes TRAF6 binding or mutations in the FHA domain that are known to abolish FHA domain binding to phosphopeptide fails to activate NFkappaBeta and c-Jun amino-terminal kinase. TIFA, when overexpressed, binds both TRAF6 and IRAK-1 and significantly enhances the IRAK-1/TRAF6 interaction. Furthermore, analysis of endogenous proteins indicates that TIFA associates with TRAF6 constitutively, whereas it associates with IRAK-1 in an IL-1 stimulation-dependent manner in vivo. Thus, TIFA is likely to mediate IRAK-1/TRAF6 interaction upon IL-1 stimulation.
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PMID:Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling. 1256 47