Role of cAMP in eukaryotic cells
Main article: function of cAMP-dependent protein kinase
cAMP and its associated kinases function in several biochemical processes, including the regulation of glycogen, sugar, and lipidmetabolism.
In eukaryotes, cyclic AMP works by activating protein kinase A ([PKA], cAMP-dependent protein kinase). PKA is normally inactive as a tetrameric holoenzyme, consisting of two catalytic and two regulatory units (C2R2), with the regulatory units blocking the catalytic centers of the catalytic units. Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus activating the catalytic units and enabling them to phosphorylatesubstrate proteins.
The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. The phosphorylated proteins may act directly on the cell's ion channels, or may become activated or inhibited enzymes. Protein kinase A can also phosphorylate specific proteins that bind to promoter regions of DNA, causing increased expression of specific genes. Not all protein kinases respond to cAMP. Several classes of protein kinases, including protein kinase C, are not cAMP-dependent.
Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell.
Still, there are some minor PKA-independent functions of cAMP, e.g., activation of calcium channels, providing a minor pathway by which growth hormone-releasing hormone causes a release of growth hormone.
However, the view that the majority of the effects of cAMP are controlled by PKA is an outdated one. In 1998 a family of cAMP-sensitive proteins with guanine nucleotide exchange factor (GEF) activity was discovered. These are termed Exchange proteins activated by cAMP (Epac) and the family comprises Epac1 and Epac2[ citation needed ]. The mechanism of activation is similar to that of PKA: the GEF domain is usually masked by the N-terminal region containing the cAMP binding domain. When cAMP binds, the domain dissociates and exposes the now-active GEF domain, allowing Epac to activate small Ras-like GTPase proteins, such as Rap1.
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