Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains

被引:347
作者
Willoughby, Debbie [1 ]
Cooper, Dermot M. F. [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England
基金
英国惠康基金;
关键词
D O I
10.1152/physrev.00049.2006
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The adenylyl cyclases are variously regulated by G protein subunits, a number of serine/threonine and tyrosine protein kinases, and Ca2+. In some physiological situations, this regulation can be readily incorporated into a hormonal cascade, controlling processes such as cardiac contractility or neurotransmitter release. However, the significance of some modes of regulation is obscure and is likely only to be apparent in explicit cellular contexts (or stages of the cell cycle). The regulation of many of the ACs by the ubiquitous second messenger Ca2+ provides an overarching mechanism for integrating the activities of these two major signaling systems. Elaborate devices have been evolved to ensure that this interaction occurs, to guarantee the fidelity of the interaction, and to insulate the microenvironment in which it occurs. Subcellular targeting, as well as a variety of scaffolding devices, is used to promote interaction of the ACs with specific signaling proteins and regulatory factors to generate privileged domains for cAMP signaling. A direct consequence of this organization is that cAMP will exhibit distinct kinetics in discrete cellular domains. A variety of means are now available to study cAMP in these domains and to dissect their components in real time in live cells. These topics are explored within the present review.
引用
收藏
页码:965 / 1010
页数:46
相关论文
共 442 条
[1]   TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling [J].
Abrahamsen, H ;
Baillie, G ;
Ngai, J ;
Vang, T ;
Nika, K ;
Ruppelt, A ;
Mustelin, T ;
Zaccolo, M ;
Houslay, M ;
Taskén, K .
JOURNAL OF IMMUNOLOGY, 2004, 173 (08) :4847-4858
[2]   RGS proteins have a signalling complex: Interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins [J].
Abramow-Newerly, M ;
Roy, AA ;
Nunn, C ;
Chidiac, P .
CELLULAR SIGNALLING, 2006, 18 (05) :579-591
[3]  
ABRAMSON L, 1991, PSYCHOL INQ, V2, P11
[4]   Functional consequences of relocating the C-terminal calmodulin-binding autoinhibitory domains of the plasma membrane Ca2+ pump near the N-terminus [J].
Adamo, HP ;
Grimaldi, ME .
BIOCHEMICAL JOURNAL, 1998, 331 :763-766
[5]   FLUORESCENCE RATIO IMAGING OF CYCLIC-AMP IN SINGLE CELLS [J].
ADAMS, SR ;
HAROOTUNIAN, AT ;
BUECHLER, YJ ;
TAYLOR, SS ;
TSIEN, RY .
NATURE, 1991, 349 (6311) :694-697
[6]   RANGE OF MESSENGER ACTION OF CALCIUM-ION AND INOSITOL 1,4,5-TRISPHOSPHATE [J].
ALLBRITTON, NL ;
MEYER, T ;
STRYER, L .
SCIENCE, 1992, 258 (5089) :1812-1815
[7]   Subcellular dynamics of protein kinase A activity visualized by FRET-based reporters [J].
Allen, Michael D. ;
Zhang, Jin .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 348 (02) :716-721
[8]  
Ambudkar Indu S, 2004, Novartis Found Symp, V258, P63
[9]   Ca2+ signaling microdomains:: platforms for the assembly and regulation of TRPC channels [J].
Ambudkar, IS .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2006, 27 (01) :25-32
[10]  
ANTONI FA, 1995, J BIOL CHEM, V270, P28055