Gβγ Transduces [Ca2+]i Oscillations and Gαq a Sustained Response during Stimulation of Pancreatic Acinar Cells with [Ca2+]i-mobilizing Agonists*

Gβγ Transduces [Ca2+]i Oscillations and Gαq a Sustained Response during Stimulation of Pancreatic Acinar Cells with [Ca2+]i-mobilizing Agonists*
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在用 [Ca2+]i 动员激动剂刺激胰腺腺泡细胞期间,Gβγ 转导 [Ca2+]i 振荡,Gαq 产生持续反应*

DOI:
--
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发表时间:
1996
影响因子:
4.8
通讯作者:
S. Muallem
S. Muallem
中科院分区:
生物学2区
文献类型:
--
作者:
W. Zeng;Xin Xu;S. Muallem

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激动剂诱发的[Ca 2 +]i信号传导中一个尚未解决的中心问题是[Ca 2 +]i振荡和持续反应的转导途径。我们发现,Gβγ信号[Ca ~(2+)]i振荡的激活和Gαq信号的激活在许多Ca ~(2+)动员激动剂的刺激过程中是一种持续的反应。因此,通过贴片移液管将纯化的Gβγ输注到胰腺腺泡细胞中,通过从内部储存的Ca 2+释放引起[Ca 2 +]i振荡,这被两个独立的Gβγ清除剂β-肾上腺素能受体激酶片段和突变的Gα i1 G203 A抑制。这些蛋白质,以及针对Gαq/11的抑制性抗体,当在细胞刺激之前应用时,可能通过阻止Gq解离成其亚基来防止[Ca 2 +]i振荡和持续反应。在细胞刺激和Gq解离成Gβγ和Gαq后,清除Gβγ可稳定持续反应并抑制拮抗剂终止细胞刺激后亚基的再结合,而清除Gαq则抑制持续反应并揭示Gβγ依赖的振荡。这些发现提供了一种一般机制,通过这种机制,Ca 2+动员激动剂可以控制[Ca 2 +]i信号的类型被转导到细胞内部。
A central unresolved question in agonist-evoked [Ca2+]i signaling is the pathway by which [Ca2+]i oscillations and a sustained response are transduced. We show here that activation of Gβγ signal [Ca2+]i oscillations and activation of Gαq signal a sustained response during stimulation by a number of Ca2+-mobilizing agonists. Thus, infusion of purified Gβγ into pancreatic acinar cells through a patch pipette evokes [Ca2+]i oscillations by Ca2+ release from internal stores, which were inhibited by two independent scavengers of Gβγ, the β-adrenergic receptor kinase fragment, and a mutated Gαi1G203A. These proteins, as well as an inhibitory antibody against Gαq/11, prevent [Ca2+]i oscillations and the sustained response when applied before cell stimulation, possibly by preventing the dissociation of Gq into its subunits. After cell stimulation and dissociation of Gq into Gβγ and Gαq, scavenging Gβγ stabilized the sustained response and inhibited reassociation of the subunits on termination of cell stimulation with antagonist, whereas scavenging Gαq inhibited the sustained response and uncovered the Gβγ-dependent oscillations. These findings provide a general mechanism by which Ca2+-mobilizing agonists can control the type of [Ca2+]i signal to be transduced to the cell interior.
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DOI: --
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影响因子: --
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