RESUMO
We have investigated the electronic and magnetic structures of Sr(2)FeMoO(6) employing site-specific direct probes, namely x-ray absorption spectroscopy with linearly and circularly polarized photons. In contrast to some previous suggestions, the results clearly establish that Fe is in the formal trivalent state in this compound. With the help of circularly polarized light, it is unambiguously shown that the moment at the Mo sites is below the limit of detection (<0.25 mu(B)), resolving a previous controversy. We also show that the decrease of the observed moment in magnetization measurements from the theoretically expected value is driven by the presence of mis-site disorder between Fe and Mo sites.
RESUMO
The stress-activated pathways leading to activation of p38 MAP kinase (p38 MAPK) and c-jun N-terminal kinases (JNK) have been shown to be activated by pro-inflammatory cytokines, physical and chemical stresses as well as a variety of hematopoietic growth factors. One exception is interleukin (IL)-4, which does not activate this pathway in hematopoietic cell. We report here that in A431, a keratinocytic cell line, IL-4 activates Rac and Cdc42 and their downstream effector p21-activated kinase (PAK). Rac and Cdc42 appear to regulate a protein kinase cascade initiated at the level of PAK and leading to activation of p38 MAPK, since IL-4 stimulates tyrosine phosphorylation of p38 MAPK and increases its catalytic activity. As A431 cells are able to produce IL-6 in response to IL-4 stimulation, we assessed the involvement of p38 MAPK in IL-6 gene expression. A pyrimidazole compound, SB203580, a specific inhibitor of p38 MAPK, inhibits production and gene expression of IL-6. SB203580 reduced significantly the stability of IL-6 mRNA. Here we provide evidence that p38 MAPK is activated in response to IL-4 and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Queratinócitos/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Interleucina-4/farmacologia , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno , Queratinócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piridinas/farmacologia , Receptores de Interleucina-4/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sequências Reguladoras de Ácido Nucleico , Fator de Transcrição STAT6 , Transativadores/genética , Transativadores/metabolismo , Transcrição Gênica , Quinases Ativadas por p21 , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Interleukin-4 (IL-4) is a pleiotropic cytokine, which acts on both hematopoietic and non-hematopoietic cells, through different types of receptor complexes. In this study, we report that in human B cells, IL-4 caused rapid phosphorylation of Janus kinase (JAK) 1 and JAK3 tyrosine kinases. In keratinocytes, the hematopoietic-specific receptor common gamma(c) chain is not expressed and the IL-13 receptor alpha(1) (IL-13Ralpha(1)) participates in IL-4 signal transduction. In keratinocytes, IL-4 induced JAK1 and JAK2 phosphorylation but, unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling. In both cell types, IL-4 induced phosphorylation and DNA binding activation of the signal transducer and activator of transcription (STAT) 6 protein. Furthermore, IL-4 stimulation of keratinocytes also induced tyrosine phosphorylation of STAT3 which was found to bind to the phosphorylated IL-13Ralpha(1). STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.
