Novel regulation of adenylyl cyclases by direct protein-protein interactions: insights from snapin and ric8a.
Adenosine 3',5'-cyclic mononucleotide (cAMP) is one of the most important second messengers which govern cellular signal transductions. Adenylyl cyclases (ACs), which are cAMP-synthesizing enzymes, are responsible for cAMP production during extracellular stimulation or intracellular metabolic alteration. In mammals, 9 transmembrane ACs and 1 soluble AC have been identified and characterized. In the past 2 decades, the biochemical properties of these ACs have been extensively studied. Genetic knockout and transgenic overexpression mouse models of at least 6 ACs have been produced, revealing their specific in vivo functions. An awareness of the importance of microdomains and cellular compartmentation for selective AC regulation has also been fostered. Most intriguingly, a handful of novel AC-binding proteins have recently been reported. Selective binding of ACs to their binding partners allows the precise compartmentalization of ACs and permits unique regulation. Based on recent studies on AC-interacting proteins (particularly Snapin and Ric8a), this review focuses on the importance and possible involvement of AC-interacting proteins in (1) the association of the cAMP signaling pathway with various cellular machineries and (2) the coordination of tightly regulated cAMP signaling by other signaling molecules.
Wang
Shyi-Chyi
SC
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
Lin
Jiun-Tsai
JT
Chern
Yijuang
Y
D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D009420:Nervous System / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C485884:Ric8a protein, mouse; C498451:Snapin protein, mouse; D033921:Vesicular Transport Proteins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases