ErbB2, a member of the receptor tyrosine kinase family, is frequently over-expressed in breast cancer. Proteolysis of the extracellular domain of ErbB2 results in constitutive activation of ErbB2 kinase. Recent study reported that ErbB2 is found in the nucleus. Here, we showed that ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. The NLS sequence KRRQQKIRKYTMRR (aa655-668) contains three clusters of basic amino acids and it is sufficient to target GFP into the nucleus. However, mutation in any basic amino acid cluster of this NLS sequence significantly affects its nuclear localization. Furthermore, it was found that this NLS is essential for the nuclear localization of ErbB2 since the intracellular domain of Erb2 lacking NLS completely abrogates its nuclear translocation. Taken together, our study identified a novel nuclear localization signal and reveals a novel mechanism underlying ErbB2 nuclear trafficking and localization.
Several epidemiological studies have investigated that Na or K intakes might be associated with the metabolic syndrome (MetS). However, little evidence has evaluated the association between Na:K ratio and the MetS. In this study, we assessed the association between the dietary Na:K ratio and the MetS. The cross-sectional study was conducted among adults aged 18 years and older in Nanjing, using a multi-stage random sampling method, which resulted in a sample size of 1993 participants. Dietary Na and K intakes were assessed by 3 consecutive days of dietary recollection combined with condiments weighing method. Health-related data were obtained by standardised questionnaires, as well as physical examinations and laboratory assessments. The prevalence rate of the MetS was 36·5 % (728/1993). After adjusting for various lifestyle and dietary factors of the MetS, participants in the highest quartile of dietary Na:K ratio were at a higher risk of developing MetS (OR=1·602; 95 % CI 1·090, 2·353) compared with those in the lowest quartile. Each 1-sd increase in dietary Na:K ratio was associated with a higher risk of prevalent MetS (OR=1·166; 95 % CI: 1·018, 1·336). Among the components of the MetS, dietary Na:K ratio was positively associated with high blood pressure (quartile 3 v. quartile 1: OR=1·656; 95 % CI 1·228, 2·256) and hypertriacylglycerolaemia (quartile 4 v. quartile1: OR=1·305; 95 % CI 1·029, 1·655) in multivariate analysis. These results revealed that higher dietary Na:K ratio significantly increased the risk of the MetS in Chinese adults. Further studies are needed to verify this association.
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