cAMP-dependent pathway

In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication. cAMP was discovered by Earl Sutherland and Ted Rall. cAMP is considered a secondary messenger along with Ca2+. Sutherland won the Nobel Prize in 1971 for his discovery of the mechanism of action of epinephrine in glycogenolysis, that requires cAMP as secondary messenger. G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins that respond to a variety of extracellular stimuli. Each GPCR binds to and is activated by a specific ligand stimulus that ranges in size from small molecule catecholamines, lipids, or neurotransmitters to large protein hormones. When a GPCR is activated by its extracellular ligand, a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein complex. The Gs alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex. In a cAMP-dependent pathway, the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP).Increases in concentration of the second messenger cAMP may lead to the activation of The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated only if cAMP is present. Once PKA is activated, it phosphorylates a number of other proteins including: Also phosphorylate AMPA Specificity of signaling between a GPCR and its ultimate molecular target through a cAMP-dependent pathway may be achieved through formation of a multiprotein complex that includes the GPCR, adenylyl cyclase, and the effector protein. In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase), one of the first few kinases discovered. It has four sub-units two catalytic and two regulatory. cAMP binds to the regulatory sub-units. It causes them to break apart from the catalytic sub-units. The Catalytic sub-units make their way in to the nucleus to influence transcription.Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell.