The regulation of AMP-activated protein kinase by phosphorylation

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阅读量：

105

作者：

SC Stein，A Woods，NA Jones，MD Davison，D Carling

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摘要：

The -activated () cascade is activated by an increase in the /ATP ratio within the cell. is regulated allosterically by and by reversible . Threonine-172 within the catalytic subunit (alpha) of ((172)) was identified as the major site phosphorylated by the -activated kinase (AMPKK) in vitro. We have used site-directed to study the role of of (172) on activity. Mutation of (172) to an (T172D) in either or resulted in a kinase complex with approx. 50% the activity of the corresponding wild-type complex. The activity of wild-type decreased by greater than 90% following treatment with protein , whereas the activity of the T172D mutant complex fell by only 10-15%. Mutation of (172) to an (T172A) almost completely abolished . These results indicate that of (172) accounts for most of the activation by AMPKK, but that other sites are involved. In support of this we have shown that AMPKK phosphorylates at least two other sites on the alpha subunit and one site on the beta subunit. Furthermore, we provide evidence that of (172) may be involved in the sensitivity of the complex to .

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关键词：

cell signalling protein kinase cascade site-directed mutagenesis two-dimensional gel electrophoresis

DOI：

10.1042/0264-6021:3450437

被引量：

1733

年份：

2000