cAMP信号转通路总结.docVIP

cAMP (Cyclic Adenosine 3,5-monophosphate) is the first identified second messenger, which has a fundamental role in the cellular response to many extracellular stimuli. The cAMP signaling pathway controls a diverse range of cellular processes. Indeed, not only did cAMP provide the paradigm for the second messenger concept, but also provided the paradigm for signaling compartmentalization. The different receptors, chiefly the GPCRs (G-Protein Coupled Receptors), Alpha and Beta-ADRs (Adrenergic Receptors), Growth Factor receptors, CRHR (Corticotropin Releasing Hormone Receptor), GcgR (Glucagon Receptor), DCC (Deleted in Colorectal Carcinoma), etc are responsible for cAMP accumulation in cells that cause different physiological outcomes, and changes in cAMP levels effects the selective activation of PKA (cAMP dependent Protein Kinase-A) isoforms. The chief source of cAMP is from ATP (Adenosine Triphosphate). In mammals, the conversion of ATP to cAMP is mediated by members of the Class-III AC (Adenylyl Cyclase)/ADCY (Adenylate Cyclase) family (E.C 4.6.1.1), which in humans comprises nine trans-membrane AC enzymes or tmACs and one soluble AC or sAC (Ref.1 2). The sAC predominantly occurs in mature spermatozoa. tmACs are regulated by heterotrimeric G-proteins in response to the stimulation of various types of GPCRs and therefore play a key role in the cellular response to extracellular signals. sAC, in contrast, is insensitive to G-proteins. Instead, sAC is directly activated by Ca2+ (Calcium Ions) and the metabolite HCO3- (Bicarbonate Ions), rendering the enzyme an intracellular metabolic sensor. Together, tmACs and sAC regulate a diverse set of essential biological processes, such as differentiation and gene transcription, and this makes cAMP signaling, an important mediator of intra- and extracellular signals in organisms from prokaryotes to higher eukaryotes (Ref.2 3). The extracellular stimuli like neurotransmitters, hormones, inflammatory stimuli, stress, epinephr