Adenosine triphosphate (ATP) release from rabbit erythrocytes occurs in response to deformation or reduced oxygen tension. A signal transduction pathway that relates these stimuli to ATP release has been proposed. This pathway includes the heterotrimeric G proteins, Gs and Gi, adenylyl cyclase, protein kinase A, and the cystic fibrosis transmembrane conductance regulator. Importantly, adenylyl ...

Ca2+-sensitive adenylyl cyclases are key integrators of Ca2+ and cAMP signaling. To selectively probe dynamic changes in [Ca2+]i at the plasma membrane where adenylyl cyclases reside, a full-length, Ca2+-inhibitable type VI adenylyl cyclase/aequorin chimera has been constructed by a two-stage polymerase chain reaction method. The expressed adenylyl cyclase/aequorin chimera was appropriately loc...

Oligomerization plays an important role in endoplasmic reticulum processing and membrane insertion (and ultimately in regulation of function) of a number of transmembrane spanning proteins. Furthermore, it is known that adenylyl cyclases (ACs), critical regulators of cellular functions, associate into higher order (dimeric) forms. However, the importance of these higher order aggregates in regu...

In addition to increasing cGMP, the soluble guanylyl cyclase (sGC) activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) can elevate intracellular cAMP levels. This response was assumed to be as a result of cGMP-dependent inhibition of cAMP phosphodiesterases; however, in this study, we show that YC-1-induced cAMP production in the rat pancreatic beta cell line INS-1E occurs independe...

G protein-coupled receptor kinases (GRKs) are thought to be important in mediating the agonist-induced phosphorylation and consequent desensitization of G protein-coupled receptor responses. NG108-15 mouse neuroblastoma X rat glioma cells express a wide range of G protein-coupled receptors and significant levels of GRK2. Therefore, to determine the role of GRK2 in agonist-induced desensitizatio...

A new Dictyostelium discoideum cyclase gene was identified that encodes a protein (sGC) with 35% similarity to mammalian soluble adenylyl cyclase (sAC). Gene disruption of sGC has no effect on adenylyl cyclase activity and results in a >10-fold reduction in guanylyl cyclase activity. The scg- null mutants show reduced chemotactic sensitivity and aggregate poorly under stringent conditions. With...

The activity of the adrenergic system plays an important role in the genesis of malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia. Acute myocardial ischemia induces an increased activity of adenylyl cyclase. This sensitization at the enzyme level as shown in the isolated perfused rat heart occurs rapidly after the onset of ischemia (5-15 minutes) and is ...

Activation of adenylyl cyclase and the consequent production of cAMP is a process that has been shown to be central to invertebrate model systems of information storage. In the vertebrate brain, it has been suggested that a presynaptic cascade involving Ca influx, cAMP production, and subsequent activation of cAMP-dependent protein kinase is necessary for induction of long-term potentiation (LT...

Ca-sensitive adenylyl cyclases may act as early integrators of the two major second messenger-signaling pathways mediated by Ca and cAMP. Ca stimulation of adenylyl cyclase type I (ACI) and adenylyl cyclase type VIII (ACVIII) is mediated by calmodulin and the site on these adenylyl cyclases that interacts with calmodulin has been defined. By contrast, the mechanism whereby Ca inhibits adenylyl ...