The NH2-terminal region of the active domain of sonic hedgehog is necessary for its signal transduction

The NH2-terminal domain of sonic hedgehog (residue 25-198) was expressed in both yeast and animal cells. The yeast-derived MH2-terminal domain of soni c hedgehog was less active by far than the animal cell-derived counterpart. The yeast-derived NH2-terminal domain of sonic hedgehog lacked 10 amino ac ids from the NH2-terminus. This cleavage of the yeast-derived NH2-terminal domain of sonic hedgehog might due to Kex 2. In contrast, a mutant yeast-de rived NH2-terminal domain of sonic hedgehog (Lys-33 to Thr) retained its NH 2-terminus and its activity was comparable to that of the animal cell-deriv ed NH2-terminal domain of sonic hedgehog, The NH2-terminal deleted NH2-term inal domain of sonic hedgehog completely lost its activity, nevertheless it inhibited the alkaline phosphatase activity induced by the animal cell-der ived NH2-terminal domain of sonic hedgehog in a dose-dependent manner. Thes e data suggest that the NH2-terminal deleted NH2-terminal domain of sonic h edgehog retains a receptor-binding ability and that the NH2-terminal peptid e of the NH2-terminal domain of sonic hedgehog is necessary for its signal transduction, (C) 1999 Federation of European Biochemical Societies.