Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase
Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase
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DOI：
10.1073/pnas.250475697
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发表时间：
2000-12-05
影响因子：
11.1
通讯作者：
Petes, TD
中科院分区：
文献类型：
--
作者：
Mallory, JC;Petes, TD
酿酒酵母蛋白Tel1p和Mec1p参与端粒长度调节和细胞对DNA损伤的反应。这些蛋白的近亲是人类共济失调毛细血管扩张突变蛋白（ATM），这是一种对wortmaninin敏感的蛋白激酶，主要磷酸化SQ基序中的丝氨酸。我们构建了含有功能表位标记的Tel1p和Mec1p的酵母菌株。我们发现免疫沉淀的Te[lp和Mec1p能够在体外磷酸化哺乳动物蛋白pase -1（磷酸化热酸稳定蛋白）。这些活动对wortmaninin很敏感。Tel1p磷酸化phas1中SQ基序中的丝氨酸。Tel1p和Mec1p激酶结构域的突变导致体外激酶活性的丧失以及与无效tell和mec1突变相关的体内表型。
The Saccharomyces cerevisiae proteins Tel1p and Mec1p are involved in telomere length regulation and cellular responses to DNA damage. The closest relative of these proteins is the human Ataxia Telangiectasia Mutated (ATM) protein, a wortmannin-sensitive protein kinase that primarily phosphorylates serines in an SQ motif. We constructed yeast strains containing functional epitopetagged Versions of Tel1p and Mec1p. We showed that immunoprecipitated Te[lp and Mec1p were capable of in vitro phosphorylation of the mammalian protein PHAS-1 (Phosphorylated Heat and Acid Stable protein). These activities are sensitive to wortmannin. Tel1p phosphorylates serine in an SQ motif in PHAS-1. Mutations in the kinase domains of Tel1p and Mec1p result in loss of in vitro kinase activity and the in vivo phenotypes associated with the null tell and mec1 mutations.