Identification of a novel AMP-activated protein kinase β subunit isoform that is highly expressed in skeletal muscle
Identification of a novel AMP-activated protein kinase β subunit isoform that is highly expressed in skeletal muscle
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DOI：
10.1074/jbc.273.20.12443
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发表时间：
1998-05-15
影响因子：
4.8
通讯作者：
Carling, D
中科院分区：
文献类型：
--
作者：
Thornton, C;Snowden, MA;Carling, D
AMP激活蛋白激酶（AMPK）是一个不断增长的相关激酶家族的成员，包括酵母中的SNF 1复合物，它对营养应激有反应。AMPK是一个催化亚基（α）和两个调节亚基（β和γ）的异源三聚体复合物，与所有三个亚基相关的蛋白质已在SNF 1复合物中鉴定。我们已经使用了双杂交系统，以确定蛋白质相互作用的催化亚基（α 2）。使用这种方法，我们已经分离出一种新的AMPK β亚型，我们命名为AMPK β 2。β 2的N-末端区域与先前表征的同种型（β 1）的N-末端区域显著不同，表明该区域可能在同种型特异性AMPK活性中发挥作用。β 1和β 2的C-末端序列与它们在酵母中的相关蛋白质的比较确定了两个高度保守的区域，预测其参与α和γ亚基的结合。在许多组织中检查β 1和β 2的表达，揭示β 1同种型在肝脏中高度表达，在骨骼肌中低表达，而β 2同种型观察到相反的模式。这些结果表明，β亚型具有组织特异性作用，这可能涉及改变上游信号和/或下游靶向AMPK复合物的反应。
The AMP-activated protein kinase (AMPK) is a member of a growing family of related kinases, including the SNF1 complex in yeast, which respond to nutritional stress. AMPK is a heterotrimeric complex of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), and proteins related to all three subunits have been identified in the SNF1 complex. We have used the two-hybrid system in order to identify proteins interacting with the catalytic subunit (alpha 2). Using this approach, we have isolated a novel AMPK beta isoform, which we designate AMPK beta 2. The N-terminal region of beta 2 differs significantly from that of the previously characterized isoform (beta 1), suggesting that this region could play a role in isoform-specific AMPK activity. Comparison of the C-terminal sequences of beta 1 and beta 2 with their related proteins in yeast identifies two highly conserved regions predicted to be involved in binding of the alpha and gamma subunits. The expression of beta 1 and beta 2 was examined in a number of tissues, revealing that the beta 1 isoform is highly expressed in liver with low expression in skeletal muscle, whereas the opposite pattern is observed for the beta 2 isoform. These results suggest that the beta isoforms have tissue-specific roles, which may involve altered responses to upstream signaling and/or downstream targeting of the AMPK complex.