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Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
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Intraspecific variation in reproductive physiology and egg quality in the European Starling Sturnus vulgaris 总被引:1,自引:0,他引:1
Egg mass shows large intraspecific variation in birds and is repeatable within individuals. The mechanisms underlying this variation are unknown. We hypothesized that measures of egg quality (the mass of yolk protein, yolk lipid, and albumen protein) would be positively correlated with the plasma pools of the yolk precursor vitellogenin, and the masses of the oviduct, metabolic machinery (liver, heart, lungs, kidneys, gizzard, small intestine and pancreas), and endogenous stores of protein and lipid. We tested these predictions in European Starlings Sturnus vulgaris collected at the peak of egg production effort. In contrast to our predictions, both yolk protein and yolk lipid were negatively correlated with plasma vitellogenin levels. Albumen protein was positively related to oviduct mass, but other aspects of body composition failed to explain variation in egg quality. Hence, while we observed correlations between egg composition and peripheral systems (circulating precursor pools and the oviduct), we found no evidence that egg quality is determined by more general processes, i.e., the supply and processing of nutrients. 相似文献
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The nucleotide sequences of the Escherichia coli genome between the glycogen biosynthetic genes glgB and glgC, and 1170 bp of DNA which follows glgA have been determined. The region between glgB and glgC contains an open reading frame (ORF) of 1521 bp which we call glgX. This ORF is capable of coding for an Mr 56 684 protein. The deduced amino acid (aa) sequence for the putative product shows significant similarity to the E. coli glycogen branching enzyme, and to several different glucan hydrolases and transferases. The regions of sequence similarity include residues which have been reported to be involved in substrate binding and catalysis by taka-amylase. This suggests that the proposed product may catalyze hydrolysis or glycosyltransferase reactions. The cloned region which follows glgA contains an incomplete ORF (1149 bp), glgY, which appears to encode 383 aa of the N terminus of glycogen phosphorylase, based upon sequence similarity with the enzyme from rabbit muscle (47% identical aa residues) and with maltodextrin phosphorylase from E. coli (37% identical aa residues). Results suggest that neither ORF is required for glycogen biosynthesis. The localization of glycogen biosynthetic and degradative genes together in a cluster may facilitate the regulation of these systems in vivo. 相似文献
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