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Cyclic adenosine monophosphate
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===Role in eukaryotic cells=== {{Main|function of cAMP-dependent protein kinase}} cAMP is associated with kinases function in several biochemical processes, including the regulation of [[glycogen]], [[sugar]], and [[lipid]] [[metabolism]].<ref>{{cite journal |vauthors=Ali ES, Hua J, Wilson CH, Tallis GA, Zhou FH, Rychkov GY, Barritt GJ |title=The glucagon-like peptide-1 analogue exendin-4 reverses impaired intracellular Ca2+ signalling in steatotic hepatocytes |journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |doi=10.1016/j.bbamcr.2016.05.006 |pmid=27178543 |volume=1863 |year=2016 |issue=9 |pages=2135β46|doi-access=free }}</ref> In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or [[cAMP-dependent protein kinase]]). PKA is normally inactive as a tetrameric [[holoenzyme]], consisting of two [[catalysis|catalytic]] and two regulatory units (C<sub>2</sub>R<sub>2</sub>), 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 enabling those catalytic units to [[phosphorylate]] substrate 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 increases in transcription. Not all protein kinases respond to cAMP. Several classes of [[protein kinase]]s, including protein kinase C, are not cAMP-dependent. Further effects mainly depend on [[function of cAMP-dependent protein kinase|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 channel]]s, 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 However, the view that the majority of the effects of cAMP are controlled by PKA is an outdated one.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 [[RAPGEF3|Epac1]] and [[RAPGEF4|Epac2]].<ref>{{cite journal|last1=Bos|first1=Johannes L.|title=Epac proteins: multi-purpose cAMP targets|journal=Trends in Biochemical Sciences|date=December 2006|volume=31|issue=12|pages=680β686|doi=10.1016/j.tibs.2006.10.002|pmid=17084085}}</ref> 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]]. ====Additional role of secreted cAMP in social amoebae==== {{See also|Fungal behavior}} In the species ''[[Dictyostelid|Dictyostelium discoideum]]'', cAMP acts outside the cell as a secreted signal. The [[chemotaxis|chemotactic]] aggregation of cells is organized by periodic waves of cAMP that propagate between cells over distances as large as several centimetres. The waves are the result of a regulated production and secretion of extracellular cAMP and a spontaneous biological oscillator that initiates the waves at centers of territories.<ref>{{Cite book|last=Anderson|first=Peter A. V.|url=https://books.google.com/books?id=vEYGCAAAQBAJ&q=In+the+species+Dictyostelium+discoideum,+cAMP+acts+outside+the+cell+as+a+secreted+signal.+The+chemotactic+aggregation+of+cells+is+organized+by+periodic+waves+of+cAMP+that+propagate+between+cells+over+distances+as+large+as+several+centimetres.+The+waves+are+the+result+of+a+regulated+production+and+secretion+of+extracellular+cAMP+and+a+spontaneous+biological+oscillator+that+initiates+the+waves+at+centers+of+territories|title=Evolution of the First Nervous Systems|date=2013-11-11|publisher=Springer Science & Business Media|isbn=978-1-4899-0921-3|language=en}}</ref>
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