[HTML][HTML] Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations
ZH Yu, J Xu, CD Walls, L Chen, S Zhang… - Journal of Biological …, 2013 - ASBMB
SHP2 is an allosteric phosphatase essential for growth factor-mediated Ras activation. Germ-
line mutations in SHP2 cause clinically similar LEOPARD and Noonan syndromes, two of
several autosomal-dominant conditions characterized by gain-of-function mutations in the
Ras pathway. Interestingly, Noonan syndrome SHP2 mutants are constitutively active,
whereas LEOPARD syndrome SHP2 mutants exhibit reduced phosphatase activity. How do
catalytically impaired LEOPARD syndrome mutants engender gain-of-function phenotypes …
line mutations in SHP2 cause clinically similar LEOPARD and Noonan syndromes, two of
several autosomal-dominant conditions characterized by gain-of-function mutations in the
Ras pathway. Interestingly, Noonan syndrome SHP2 mutants are constitutively active,
whereas LEOPARD syndrome SHP2 mutants exhibit reduced phosphatase activity. How do
catalytically impaired LEOPARD syndrome mutants engender gain-of-function phenotypes …