双过氧钒化合物是有效的PTEN抑制剂。

Bisperoxovanadium compounds are potent PTEN inhibitors.

作者信息

Schmid Annette C, Byrne Richard D, Vilar Ramón, Woscholski Rüdiger

机构信息

Department of Biological Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

出版信息

FEBS Lett. 2004 May 21;566(1-3):35-8. doi: 10.1016/j.febslet.2004.03.102.

DOI:10.1016/j.febslet.2004.03.102

PMID:15147864

Abstract

The tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) shares homology with protein tyrosine phosphatases (PTPases). Similarly, bisperoxovanadium (bpV) molecules that are well-established PTPase inhibitors were shown to inhibit PTEN, but at up to 100-fold lower concentrations. The preference and potency of the bpVs towards PTEN was validated in vivo as demonstrated by: (i) an increase of Ser473 phosphorylation of protein kinase B (PKB) at similar low nanomolar doses, (ii) the lack of any effect on the PKB phosphorylation in the PTEN negative cell line UM-UC-3, (iii) the ability to rescue Ly294002-induced phosphoinositide 3-kinase inhibition and (iv) a lack of tyrosine phosphorylation at low nanomolar doses.

摘要

肿瘤抑制因子10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）与蛋白酪氨酸磷酸酶（PTPases）具有同源性。同样，作为成熟的PTPase抑制剂的双过氧钒（bpV）分子已被证明可抑制PTEN，但所需浓度要低100倍。bpV对PTEN的偏好性和效力在体内得到了验证，如下所示：（i）在相似的低纳摩尔剂量下，蛋白激酶B（PKB）的Ser473磷酸化增加；（ii）对PTEN阴性细胞系UM-UC-3中的PKB磷酸化没有任何影响；（iii）能够挽救Ly294002诱导的磷酸肌醇3激酶抑制作用；（iv）在低纳摩尔剂量下没有酪氨酸磷酸化。