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FEBS Lett. 2006 May 1;580(10):2477-82. Epub 2006 Apr 12.

Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1.

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1
INSERM U745, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.

Abstract

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.

PMID:
16638574
DOI:
10.1016/j.febslet.2006.03.088
[Indexed for MEDLINE]
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