Impact of phosphodiesterase 4D on cardiac β2 adrenergic receptor signaling

Andrew J. Patterson MD, PhD, Nathan Pearl, Christine Chang
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Abstract

Cyclic adenosine monophosphate (cAMP) is an important intracellular second messenger whose levels are tightly regulated within intracellular subdomains. Generation, detection, and degradation of cAMP is influenced by signaling complexes localized to specific regions of the cell by scaffolding proteins, such as muscle A kinase-anchoring protein (mAKAP). The distribution of cAMP within myocytes differs after β1 adrenergic receptor (β1AR) activation relative to β2AR activation as a result of differences in the interaction of these receptor subtypes with signaling complexes. β1AR stimulation generates a global increase in cAMP, whereas β2AR stimulation elicits a cAMP increase only within restricted areas of the cell. Phosphodiesterase 4D (PDE4D) plays an important role in this process.

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磷酸二酯酶4D对心脏β2肾上腺素能受体信号传导的影响
环腺苷一磷酸(cAMP)是细胞内重要的第二信使,其水平在细胞内亚域内受到严格调控。cAMP的产生、检测和降解受到定位于细胞特定区域的信号复合物的影响,这些信号复合物由支架蛋白(如肌A激酶锚定蛋白(mAKAP))构成。β1肾上腺素能受体(β1AR)激活后,cAMP在肌细胞内的分布与β2AR激活后不同,这是由于这些受体亚型与信号复合物相互作用的差异。β1AR刺激产生cAMP的全局增加,而β2AR刺激仅在细胞的有限区域内引起cAMP的增加。磷酸二酯酶4D (PDE4D)在这一过程中起重要作用。
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