Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown

被引：340

作者：

Houslay, Miles D. ^{[1
]}

机构：

[1] Univ Glasgow, FBLS, Glasgow G12 8QQ, Lanark, Scotland

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2010年 / 35卷 / 02期

基金：

英国医学研究理事会;

关键词：

PROTEIN-KINASE-A; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; N-TERMINAL REGION; BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTORS; MEMBRANE ASSOCIATION; ANCHORING PROTEINS; SCAFFOLD PROTEINS; ADENYLYL CYCLASES; CARDIAC MYOCYTES;

D O I：

10.1016/j.tibs.2009.09.007

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：

It is becoming increasingly apparent that spatial regulation of cell signalling processes is critical to normal cellular function. In this regard, cAMP signalling regulates many pivotal cellular processes and has provided the paradigm for signal compartmentalization. Recent advances show that isoforms of the cAMP-degrading phosphodiesterase-4 (PDE4) family are targeted to discrete signalling complexes. There they sculpt local cAMP gradients that can be detected by genetically encoded cAMP sensors, and gate the activation of spatially localized signalling through sequestered PKA and EPAC sub-populations. Genes for these important regulatory enzymes are linked to schizophrenia, stroke and asthma, thus indicating the therapeutic potential that selective inhibitors could have as anti-inflammatory, anti-depressant and cognitive enhancer agents.

引用

页码：91 / 100

页数：10

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