Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized ...

Recent studies identified c-di-GMP as a universal bacterial secondary messenger regulating biofilm formation, motility, production of extracellular polysaccharide and multicellular behavior in diverse bacteria. However, except for cellulose synthase, no protein has been shown to bind c-di-GMP and the targets for c-di-GMP action remain unknown. Here we report identification of the PilZ ("pills")...

Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. In thi...

Potassium and norepinephrine stimulate the efflux of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) from intact pineal glands. The postsynaptic beta-adrenergic receptor mediates the efflux of cyclic AMP. In contrast, the efflux of cyclic GMP requires calcium and intact nerve endings. It appears that sympathetic nerve endings may release cyclic GMP into...

To determine the effect of cyclic GMP and cyclic GMPdependent protein kinase, microsomes were preincubated for 10 min at 37°C with 100 pM-isobutylmethylxanthine, 1 pM-cyclic GMP alone, 16-138 p-units of cGMP-dependent protein kinase/ml alone or with the combination of these agents. Steady-state, ATP-dependent Ca? + accumulation into preparations sonicated with histamine amounted to 47 k 6 nmol/...

Atopic dermatitis (AD) is one of the most common skin diseases, whose incidence is increasing in industrialized countries. The epicutaneous application of a hapten, such as 2,4-dinitrochlorobenzene (DNCB), evokes an experimental murine AD-like reaction. Glycomacropeptide (GMP) is a dairy bioactive peptide derived from hydrolysis of κ-casein by chymosin action. It has anti-inflammatory, prebioti...

10 Bacteria live predominantly in biofilms, and the internal signal cyclic diguanylate (c-di-GMP) is an universal signal that governs the formation and the dispersal of these communities. Pseudomonas aeruginosa is one of the most important reference systems for studying bacterial biofilms and contains numerous diguanylate cyclases (DGCs) for synthesizing c-di-GMP and phosphodiesterases (PDEs) f...

The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intra...

The selective discharge of lysosome granule enzymes from human neutrophils by certain immunologic stimuli can be influenced in opposing directions by guanosine 3', 5'-monophosphate (cyclic GMP) 1 and adenosine 3', 5'-monophosphate (cyclic AMP) (1-3). Similarly, the immunologic secretion of lysosomal enzymes can be enhanced or inhibited by specific autonomic neurohormones (1-3). In fact, certain...