Reducing blood glucose level in TIDM mice by orally administering the silk glands of transgenic hIGF-I silkworms

Protein O-mannosyltransferase 1 (POMT1) and its homolog, POMT2, are responsible for the catalysis of the first step in O-mannosyl glycan synthesis. Mutations in their genes are associated with a type of congenital muscular dystrophy called Walker-Warburg syndrome. Arg⁶⁴, Glu⁷⁸ and Arg¹³⁸ in the N-terminus region of ScPmt1p, a POMT homolog in Saccharomyces cerevisiae, are important for transferase activity. Arg¹³⁸ is also essential for complex formation with ScPmt2p. Here we examined the effects of replacing the corresponding residues in human POMT1 and POMT2 with Ala on complex formation and enzymatic activity. The human POMT1 mutants lost almost all transferase activity while the POMT2 mutants retained enzymatic activity. Neither mutant lost its ability to form complexes with the native counter component. These results indicate that ScPmtps and human POMTs have different mechanisms of complex formation. They also suggest that human POMT1 and POMT2 have discrete functions since the effect of amino acid substitutions on enzymatic activity are different.