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Signal transduction through G alpha(q) involves stimulation of phospholipase C beta (PLC beta) that results in increased intracellular Ca2+ and activation of protein kinase C. We have measured complex formation between G alpha(q) and PLC beta1 in vitro and in living PC12 and HEK293 cells by fluorescence resonance energy transfer. In vitro measurements show that PLC beta1 will bind to G alpha(q)(guanosine 5'-3-O-(thio)triphosphate) and also to G alpha(q)(GDP), and the latter association has a different protein-protein orientation. In cells, image analysis of fluorescent-tagged proteins shows that G alpha(q) is localized almost entirely to the plasma membrane, whereas PLC beta1 has a significant cytosolic population. By using fluorescence resonance energy transfer, we found that these proteins are pre-associated in the unstimulated state in PC12 and HEK293 cells. By determining the cellular levels of the two proteins in transfected versus nontransfected cells, we found that under our conditions overexpression should not significantly promote complex formation. G alpha(q)-PLC beta1 complexes are observed in both single cell measurements and measurements of a large (i.e. 10(6)) cell suspension. The high level (approximately 40% maximum) of FRET is surprising considering that G alpha(q) is more highly expressed than PLC beta1 and that not all PLC beta1 is plasma membrane-localized. Our measurements suggest a model in which G proteins and effectors can exist in stable complexes prior to activation and that activation is achieved through changes in intermolecular interactions rather than diffusion and association. These pre-formed complexes in turn give rise to rapid, localized signals. 相似文献
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Flintoft L 《Nature reviews. Genetics》2011,12(4):228-229
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Timothy P. Shiau Eddy Low Bum Kim Eric D. Turtle Charles Francavilla Donogh J.R. O’Mahony Lisa Friedman Louisa D’Lima Andreas Jekle Dmitri Debabov Meghan Zuck Nichole J. Alvarez Mark Anderson Ramin Najafi Rakesh K. Jain 《Bioorganic & medicinal chemistry letters》2013,23(20):5650-5653
The discovery and development of antimicrobial agents that do not give rise to resistance remains an ongoing challenge. Our efforts in this regard continue to reveal new potential therapeutic agents with differing physicochemical properties while retaining the effective N,N-dichloroamine pharmacophore as the key antimicrobial warhead. In this Letter, we disclose agents containing polyol units as a water solubilizing group. These sulfonyl-polyol agents show broad spectrum bactericidal and virucidal activity. These compounds show 1h MBC’s of 16–512 μg/mL against Escherichia coli and 4–256 μg/mL against Staphylococcus aureus at neutral pH, and 1-h IC50’s of 4.5–32 μM against Adenovirus 5 and 0.7–3.0 μM against Herpes simplex virus 1. The lead compounds were tested in a tissue culture irritancy assay and showed only minimal irritation at the highest concentrations tested. 相似文献
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Maintaining balance with intestinal flora is an important activity of the immune system in higher metazoans. In this issue of Developmental Cell, Ha et al. demonstrate a central role of a redox balance in microbial interactions in the fruit fly gut. 相似文献