Hanna Nadine, Montagner Alexandra, Lee Wen Hwa, Miteva Maria, Vidal Michel, Vidaud Michel, Parfait Béatrice, Raynal Patrick
INSERM U745, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
FEBS Lett. 2006 May 1;580(10):2477-82. doi: 10.1016/j.febslet.2006.03.088. Epub 2006 Apr 12.
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.
豹皮综合征（LS）和努南综合征（NS）是与SHP-2不同突变相关的重叠综合征。虽然NS突变增强了SHP-2的催化活性，但我们发现，当使用标准蛋白酪氨酸磷酸酶（PTP）底物进行检测时，三种代表性LS突变体的活性无法检测到。使用特定SHP-2底物的不同检测方法证实了它们降低的PTP活性，但也揭示了T468M突变体具有显著活性。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Gab1/PI3K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表现出降低的PTP活性。
