![]() ![]() cAMP is degraded by phosphodiesterases (PDEs) that catalyze the hydrolysis of the 3' linkage (marked with arrowhead), leaving adenosine 5' phosphate (not shown). The inset shows the synthesis of cAMP by ACs, which catalyze conversion of ATP into cAMP and inorganic pyrophosphate while linking the remaining 5' phosphate with the 3' ribose carbon. These cAMP-binding proteins may themselves be effector proteins, such as transcription factors or cyclic nucleotide gated channel (CNG) proteins, or they may be intermediaries, such as the regulatory subunits of PKA, which control activation of effector proteins further downstream. cAMP then relays the signal to downstream effector proteins (DEP) either directly or indirectly by allosterically activating one or more cAMP-binding proteins. Indirect activation pathways often involve membrane receptors that transmit extracellular signals to the AC by a phosphorylation event, although other cytoplasmic factors (“Factor X” in the figure) may also be required. Downstream regulatory effects of cAMP are mediated through its allosteric interactions with cAMP-binding proteins, whose activation states are altered by conformational changes that are induced upon cAMP binding.ĬAMP relays environmental signals to regulatory outcomesĪdenylyl cyclases (ACs) can be directly or indirectly activated at the post-translational level by a number of environmental signals. However, the well-studied bacterial AC from Escherichia coli belongs to Class I. ![]() Class III is the largest and most diverse group of cyclases, and it includes all known ACs from eukaryotes, as well as many bacterial ACs 7, 13, 14, 15. ACs are divided into six classes based on primary amino acid sequences. cAMP is generated from ATP by adenylyl cyclases (ACs), while phosphodiesterases (PDEs) catalyze its hydrolytic degradation ( Figure 1). The cyclic nucleotide adenosine 3'-5' cyclic monophosphate (cAMP) was the first second messenger to be described, and it is also the most broadly used by organisms. Second messengers include such diverse molecules as cyclic nucleotides, (p)ppGpp, Ca 2+, inositoltriphosphate and diacylglycerol 7, 8– 9– 12. However, many environmental signaling pathways rely on 'second messenger' molecules to relay external signals from membrane receptors to one or more effectors within the cell. Some of these molecules, such as the hormone-like acyl homoserine lactone (AHL) autoinducers that control quorum sensing in gram negative bacteria, diffuse across cell membranes from the extracellular millieu to directly control gene expression 5. This signaling is mediated by a vast array of small soluble signaling molecules, both within and outside of cells 5, 6. All organisms must respond to changing environments, and the signal transduction pathways that allow them to do so on a cellular level are essential for the control of processes ranging from chemotaxis to differentiation and apoptosis 1– 4. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |