Modulation of signaling through GPCR-cAMP-PKA pathways by PDE4 depends on stimulus intensity: Possible implications for the pathogenesis of acrodysostosis without hormone resistance

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• 作者：Emmanuelle Motte^a ; Catherine Le Stunff^a ; Claire Briet^a ; Nicolas Dumaz^b ; Caroline Silve^a ; ^c ; ^d ; ^{caroline.silve@inserm.fr}
• 关键词：cAMP ; PDE4D ; Acrodysostosis ; BRET ; Inhibition ; Hormonal response
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：442
• 期：Complete
• 页码：1-11
• 全文大小：2062 K
• 卷排序：442

文摘

The strength of the signal initiating ligand-induced cAMP accumulation is inversely correlated to the extent that inhibition of PDE4 further increased cAMP accumulation and signaling. The intensity of ligand-induced signaling through a given GPCR is cell type dependent. The intensity of the initial stimulus is a major determinant of the ability of PDE4 to attenuate the subsequent response. Thus, PDE4D mutations resulting in inappropriately increased activity may impair some, but not all, responses transmitted through GPCR-Gsα-PKA pathways in a cell type dependent manner.