Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1
Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1
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DOI：
10.1016/j.febslet.2006.03.088
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发表时间：
2006-05-01
期刊：
影响因子：
3.5
通讯作者：
Raynal, Patrick
中科院分区：
文献类型：
--
作者：
Hanna, Nadine;Montagner, Alexandra;Raynal, Patrick
LEOPARD（LS）和努南（NS）是与SHP-2不同突变相关的重叠综合征。而NS突变增强SHP-2的催化活性，我们表明，三个代表性的LS突变体的活性是不可检测的，当使用标准的蛋白酪氨酸磷酸酶（PTP）底物进行测定。使用特定SHP-2底物的不同测定证实了它们降低的PTP活性，但也揭示了T468 M突变体的显著活性。在用表皮生长因子刺激的转染细胞中，活性最低的LS突变体促进Gab 1/PI 3 K结合，验证了我们的体外数据。因此，LS突变体在体外和转染细胞中均显示出降低的PTP活性。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
LEOPARD (LS) and Noonan (NS) are overlapping syndromes associated with distinct mutations of SHP-2. Whereas NS mutations enhance SHP-2 catalytic activity, we show that the activity of three representative LS mutants is undetectable when assayed using a standard protein tyrosine phosphatase (PTP) substrate. A different assay using a specific SHP-2 substrate confirms their decreased PTP activity, but also reveals a significant activity of the T468M mutant. In transfected cells stimulated with epidermal growth factor, the least active LS mutants promote Gab1/PI3K binding, validating our in vitro data. LS mutants thus display a reduced PTP activity both in vitro and in transfected cells. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.