[Mode of action of cyclic amp in prokaryotes and eukaryotes, CAP and cAMP-dependent protein kinases].
cAMP is an ubiquitous compound which is involved in the regulation of many biological processes. In bacteria such as E. coli, cAMP mediates the activation of catabolic operons via the CAP protein. The CAP-cAMP complex, whose tridimensional structure has recently been established, binds to the promoter regions of catabolic operons at a specific site, and activates their transcription by inducing RNA polymerase to bind and initiate transcription at the correct site. Various phenomenons including protein-protein interactions or CAP-induced DNA bending or kinking could be involved in the process of forming the open transcription complex. In eukaryotes, cAMP activates cAMP dependent protein kinases which covalently modify proteins by phosphorylation on serine or threonine residues. The catalytically inactive holoenzyme is generally a tetramer containing two regulatory subunits, each capable of binding two molecules of cAMP, and two catalytic subunits. In mammalian cells, two types of cAMP dependent protein kinases (I and II) can be distinguished on the basis of their regulatory subunits; their relative proportion varies from tissue to tissue. Binding of cAMP to the regulatory subunits induces the dissociation of the holoenzyme and releases the free and active catalytic subunits. Phosphorylation of proteins occurs at sequences containing two basic residues in the vicinity of the phosphorylated serine or threonine. A heat-stable protein, present in most eukaryotic cells, specifically interacts with the catalytic subunit and inhibits its activity. The amino-acid sequence of cAMP dependent protein kinases has recently been determined. It is interesting to note that the domains responsible for cAMP binding by the regulatory subunits of mammalian cAMP dependent protein kinases and CAP share important sequence homologies. The same phenomenon is observed concerning the domain responsible for ATP binding to the catalytic subunit of cAMP dependent protein kinases and that of tyrosine-specific protein kinases from oncoviruses. Other eukaryotic proteins such as S-adenosyl-L-homocysteine (SAH) hydrolase are also capable of binding cAMP. The latter is involved in the regulation of S-adenosyl-L-methionine dependent methylations, and its activity could be affected by cAMP. Besides its role as an effector of enzymatic activity via phosphorylation, such as in the regulation of glycogen metabolism, cAMP has recently been shown to activate the transcription of a number of eukaryotic genes. This process probably also involves protein phosphorylation, but its precise mechanism remains to be understood.
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de Gunzburg
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002477:Cells / Q000378:metabolism*; D003460:Crystallization; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism*; D005658:Fungi / Q000201:enzymology; D006003:Glycogen / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D007763:Lac Operon; D046911:Macromolecular Substances; D008970:Molecular Weight; D009132:Muscles / Q000378:metabolism; D010446:Peptide Fragments; D010766:Phosphorylation; D011387:Prokaryotic Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000502:physiology*; D012996:Solutions; D014018:Tissue Distribution; D014158:Transcription, Genetic
D004269:DNA, Bacterial; D000939:Epitopes; D007527:Isoenzymes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011953:Receptors, Cyclic AMP; D012996:Solutions; D000255:Adenosine Triphosphate; D006003:Glycogen; D000242:Cyclic AMP; D011494:Protein Kinases; D012321:DNA-Directed RNA Polymerases; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000262:Adenylyl Cyclases
Le mode d'action de l'AMP cyclique chez les procaryotes et les eucaryotes, CAP et protéine kinases AMPc dépendantes.