Activator of G protein signaling 3 forms a complex with resistance to inhibitors of cholinesterase-8A without promoting nucleotide exchange on Gαi3

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• 作者：Man K. Tse ; Christina J. Morris ; Mingjie Zhang…
• 关键词：AGS3 ; GPSM1 ; Ric ; 8A ; GEF ; cAMP
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：401
• 期：1-2
• 页码：27-38
• 全文大小：1,768 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

Activator of G protein signaling 3 (AGS3) is a guanine nucleotide dissociation inhibitor (GDI) which stabilizes the Gαi/o subunits as an AGS3/Gαi/o-GDP complex. It has recently been demonstrated in reconstitution experiments that the AGS3/Gαi/o-GDP complex may act as a substrate of resistance to inhibitors of cholinesterase 8A (Ric-8A), a guanine exchange factor (GEF) for heterotrimeric Gα proteins. Since the ability of Ric-8A to activate Gαi/o subunits that are bound to AGS3 in a cellular environment has not been confirmed, we thus examined the effect of Ric-8A on cAMP accumulation in HEK293 cells expressing different forms of AGS3 and Gαi3. Co-immunoprecipitation assays indicate that full-length AGS3 and its N- and C-terminal truncated mutants can interact with Ric-8A in HEK293 cells. Yeast two-hybrid assay further confirmed that Ric-8A can directly bind to AGS3S, a short form of AGS3 which is endogenously expressed in heart. However, Ric-8A failed to facilitate Gαi-induced suppression of adenylyl cyclase, suggesting that it may not serve as a GEF for AGS3/Gαi/o-GDP complex in a cellular environment.