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The NH 2 ‐terminal region of the active domain of sonic hedgehog is necessary for its signal transduction

1999; Wiley; Volume: 447; Issue: 2-3 Linguagem: Inglês

10.1016/s0014-5793(99)00300-2

1873-3468

Mieko Katsuura, Yoshiko Hosono-Sakuma, Masako Wagatsuma, Sachiko Yanagisawa, Makoto Okazaki, M Kimura,

Epigenetics and DNA Methylation

The NH2-terminal domain of sonic hedgehog (residue 25-198) was expressed in both yeast and animal cells. The yeast-derived NH2-terminal domain of sonic hedgehog was less active by far than the animal cell-derived counterpart. The yeast-derived NH2-terminal domain of sonic hedgehog lacked 10 amino acids 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-derived NH2-terminal domain of sonic hedgehog (Lys-33 to Thr) retained its NH2-terminus and its activity was comparable to that of the animal cell-derived NH2-terminal domain of sonic hedgehog. The NH2-terminal deleted NH2-terminal domain of sonic hedgehog completely lost its activity, nevertheless it inhibited the alkaline phosphatase activity induced by the animal cell-derived NH2-terminal domain of sonic hedgehog in a dose-dependent manner. These data suggest that the NH2-terminal deleted NH2-terminal domain of sonic hedgehog retains a receptor-binding ability and that the NH2-terminal peptide of the NH2-terminal domain of sonic hedgehog is necessary for its signal transduction.