Type I and type VIII adenylyl cyclases constitute a family whose activation is coupled to cellular deformation through the action of calcium-calmodulin.

Type I and type VIII adenylyl cyclases constitute a family whose activation is coupled to cellular deformation through the action of calcium-calmodulin.
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I 型和 VIII 型腺苷酸环化酶构成一个家族,其激活通过钙-钙调蛋白的作用与细胞变形相关。

DOI:
10.1139/o95-044
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发表时间:
1995
期刊:
Biochemistry and cell biology = Biochimie et biologie cellulaire
影响因子:
--
通讯作者:
Kempinski,AM
Kempinski,AM
中科院分区:
--
文献类型:
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作者:
Watson,PA;Giger,KE;Kempinski,AM

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在某些组织和细胞中,第二信使cAMP浓度增加是对机械或变形刺激的反应。人胚胎肾(HEK)293细胞稳定表达I型和VIII型腺酰环化酶,它们是钙调素刺激的腺酰环化酶家族的成员。外源表达I型腺酰环化酶或三种VIII型腺酰环化酶剪接变异体的HEK 293细胞对肿胀的反应是cAMP增加,这需要细胞外介质中存在钙来实现这种反应。表达VII型cAMP的HEK293细胞对肿胀无反应,但能增强异丙肾上腺素刺激的活性。这是蛋白激酶C对III型蛋白活性的影响的特征。表达腺酰环化酶剪接变异体的HEK293细胞的相对肿胀反应性与这些剪接变异体的钙-钙调蛋白刺激的相对EC50值一致。这与钙调蛋白的参与和细胞内钙的增加在介导肿胀诱导的VIII型腺酰环化酶活性加速中的作用是一致的。关键词:机械转导,cAMP,钙,钙调蛋白,细胞骨架。
In certain tissues and cells, increases in concentrations of the second messenger cAMP are seen in response to mechanical or deformational stimuli. Type I and type VIII adenylyl cyclases, representing members of a family of calcium–calmodulin-stimulated adenylyl cyclases, and type VII adenylyl cyclase were each stably expressed in human embryonal kidney (HEK) 293 cells. HEK 293 cells exogenously expressing either type I adenylyl cyclase or any one of three type VIII adenylyl cyclase splice variants respond to swelling with increases in cAMP, requiring the presence of calcium in the extracellular medium for such responsiveness. Type VII expressing HEK 293 cells failed to respond to swelling with increased cAMP but demonstrated potentiationof isoproterenol-stimulated activity. This is characteristic of the influence of protein kinase C on the activity of the type VII protein. The relative swelling responsiveness of HEK 293 cells expressing splice variants of the type VIII adenylyl cyclase is consistent with the relative EC50values for calcium–calmodulin stimulation of these splice variants. This is consistent with the involvement of calmodulin and the requirement for increases in intracellular calcium in mediating swelling-induced acceleration of type VIII adenylyl cyclase activity.Key words: mechanotransduction, cAMP, calcium, calmodulin, cytoskeleton.