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Amira Alkharusi Elena Lesma Silvia Ancona Eloisa Chiaramonte Thomas Nystr?m Alfredo Gorio Gunnar Norstedt 《PloS one》2016,11(1)
Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects. 相似文献
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Cindy H. Wu Thomas K. Wood Ashok Mulchandani Wilfred Chen 《Applied microbiology》2006,72(2):1129-1134
The use of plants for rehabilitation of heavy-metal-contaminated environments is an emerging area of interest because it provides an ecologically sound and safe method for restoration and remediation. Although a number of plant species are capable of hyperaccumulation of heavy metals, the technology is not applicable for remediating sites with multiple contaminants. A clever solution is to combine the advantages of microbe-plant symbiosis within the plant rhizosphere into an effective cleanup technology. We demonstrated that expression of a metal-binding peptide (EC20) in a rhizobacterium, Pseudomonas putida 06909, not only improved cadmium binding but also alleviated the cellular toxicity of cadmium. More importantly, inoculation of sunflower roots with the engineered rhizobacterium resulted in a marked decrease in cadmium phytotoxicity and a 40% increase in cadmium accumulation in the plant root. Owing to the significantly improved growth characteristics of both the rhizobacterium and plant, the use of EC20-expressing P. putida endowed with organic-degrading capabilities may be a promising strategy to remediate mixed organic-metal-contaminated sites. 相似文献
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The N-terminus of Ciona intestinalis (Ci-VSP) is a voltage-sensing domain (VSD) controlling the activity of a phosphatase domain on the C terminus. By replacing the phosphatase domain with a tandem of fluorescent proteins, CFP and YFP, a family of fluorescence resonance energy transfer-based, genetically encoded voltage-sensing fluorescent protein (VSFP) was created. VSFP2.3, one of the latest versions of this family, showed large changes in YFP emission upon changes in membrane potential with CFP excitation when expressed in Xenopus laevis oocytes. The time course of the fluorescence has two components: the fast component correlates with the time course of sensing current produced by the charge movement, while the slow component is at least one order-of-magnitude slower than the sensing current. This suggests that the tandem of fluorescent proteins reports a secondary conformational transition of the VSD which resembles the relaxation of the VSD of Ci-VSP described in detail for the Ci-VSP. This observation indicates that the relaxation of the VSD of VSFP2.3 is a global conformational change that encompasses the entire S4 segment. 相似文献
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Amino acids are widely used waterborne olfactory stimuli proposed to serve as cues in the search for food. In natural waters the main source of amino acids is the decomposition of proteins. But this process also produces a variety of small peptides as intermediate cleavage products. In the present study we tested whether amino acids actually are the natural and adequate stimuli for the olfactory receptors they bind to. Alternatively, these olfactory receptors could be peptide receptors which also bind amino acids though at lower affinity. Employing calcium imaging in acute slices of the main olfactory epithelium of the fully aquatic larvae of Xenopus laevis we show that amino acids, and not peptides, are more effective waterborne odorants. 相似文献