Compartmentalization of adenylate cyclase and cAMP signalling

被引:89
作者
Cooper, DMF [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England
关键词
adenylate cyclase; A-kinase anchoring protein (AKAP); calmodulin; capacitative Ca2+ entry (CCE); cyclic nucleotide-gated channel (CNG channel); lipid raft;
D O I
10.1042/BST0331319
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Concepts of cAMP signalling have changed dramatically from the linear cascades of just a few years ago, with the realization that numerous cellular processes affect this motif. These influences include other signalling pathways - most significantly Ca2+, scaffolding proteins (which are themselves variously regulated) to organize the elements of the pathway, and subcellular targeting of components. An obvious implication of this organization is that global measurements of cAMP may trivialize the complexity of the cAMP signals and obscure the regulation of targets. In this presentation, current developments on the targeting and assembly of ACs (adenylate cyclases) and their delivery to selected raft or non-raft domains of the plasma membrane will be discussed, along with the susceptibility of raft-targeted ACs to very discrete modes of increases in the intracellular Ca2+ concentration. Single-cell explorations of cAMP dynamics, as measured with cyclic nucleotide-gated channels, are also described in this paper, particularly as applied to cells in which the composition of AKAP (A-kinase anchoring protein)-PKA (protein kinase A)-PDE (phosphodiesterase) assemblies is probed by RNA interference ablation of defined AKAPs.
引用
收藏
页码:1319 / 1322
页数:4
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