Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dictyostelium cells use extracellular cyclic AMP both as a chemoattractant and as a morphogen inducing cell-type-specific gene expression. Cyclic AMP binds to surface receptors, activates one or more G-proteins, and stimulates adenylate cyclase, guanylate cyclase and phosphoinositidase C. Mutant fgdC showed aberrant chemotaxis, and was devoid of cyclic AMP-induced gene expression and differentiation. Both the receptor- and G-protein-mediated stimulation of adenylate cyclase and guanylate cyclase were unaltered in mutant fgdC as compared to wild-type cells. In wild-type cells phosphoinositidase C was activated about twofold by the cyclic AMP receptor. In mutant fgdC cells, however, the enzyme was inhibited by about 60%. These results suggest that phosphoinositidase C is regulated by a receptor-operated activation/inhibition switch that is defective in mutant fgdC. We conclude that activation of phosphoinositidase C is essential for Dictyostelium development.
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PMID:Abberant chemotaxis and differentiation in Dictyostelium mutant fgdC with a defective regulation of receptor-stimulated phosphoinositidase C. 166 62

Malaria-causing parasites are transmitted from humans to mosquitoes when developmentally arrested gametocytes are taken up by a female Anopheles during a blood meal. The changes in environment from human to mosquito activate gametogenesis, including a drop in temperature, a rise in pH, and a mosquito-derived molecule, xanthurenic acid. Signaling receptors have not been identified in malaria parasites but mounting evidence indicates that cGMP homeostasis is key to sensing extracellular cues in gametocytes. Low levels of cGMP maintained by phosphodiesterases prevent precocious activation of gametocytes in the human blood. Upon ingestion, initiation of gametogenesis depends on the activation of a hybrid guanylyl cyclase/P4-ATPase. Elevated cGMP levels lead to the rapid mobilization of intracellular calcium that relies upon the activation of both cGMP-dependent protein kinase and phosphoinositide phospholipase C. Once calcium is released, a cascade of phosphorylation events mediated by calcium-dependent protein kinases and phosphatases regulates the cellular processes required for gamete formation. cGMP signaling also triggers timely egress from the host cell at other life cycle stages of malaria parasites and in Toxoplasma gondii, a related apicomplexan parasite. This suggests that cGMP signaling is a versatile platform transducing external cues into calcium signals at important decision points in the life cycle of apicomplexan parasites.
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PMID:cGMP homeostasis in malaria parasites-The key to perceiving and integrating environmental changes during transmission to the mosquito. 3311 60