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蛋白激酶A定蛋白mAKAP协调两个集成的cAMP效应器通路

Kimberly L Dodge-Kafka¹, Joseph Soughayer, Genevieve C Pare

¹Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, Oregon 97239, USA.

|September 24, 2005

概括

肌肉细胞使用mAKAP来定信号蛋白,产生局部循环腺3

科学领域:

分子生物学分子生物学
细胞信号传输细胞信号传输
生物化学生物化学

背景情况:

循环腺3',5'-单酸盐 (cAMP) 是一个重要的细胞内信使.
cAMP调节蛋白激酶 (PKA),离子通道和关氨酸核酸交换因子 (Epacs).
基化酶 (PDEs) 代谢cAMP,控制其局部度.

研究的目的:

为了识别和表征一个cAMP响应的信号复合体,该复合体被肌肉特定的A-激酶定蛋白 (mAKAP) 定.
阐明PKA,PDE4D3和Epac1在mAKAP复合体中的作用.
研究这个复合体在心肌细胞信号传递中的功能后果.

主要方法:

同免疫沉以确定mAKAP复合体内的蛋白相互作用.
药理学和分子操纵来改变信号通路.
评估心肌细胞缩作为一个功能性读数.

主要成果:

确定了一个涉及mAKAP,PKA,PDE4D3和Epac1的信号复合体.
固定PKA激活PDE4D3,减少局部cAMP,而ERK5抑制PDE4D3.
PDE4D3招募Epac1,使ERK5的cAMP依赖衰减成为可能,这可以诱导心肌细胞缩.

结论:

mAKAP复合体协调两个合的cAMP依赖的反循环.
通过AKAP蛋白质对cAMP信号的局部控制是复杂的,涉及复杂的反机制.
在mAKAP复合体内定ERK5信号,有助于心肌细胞增大.

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