Caspase 2
A key function of human granzyme
B (GrB) is to induce apoptosis of target cells, in conjunction with perforin.
The RAH allele is the first documented variant of the human GrB gene, and
occurs at frequency of 25-30%. It encodes three amino acid substitutions (Q48R,
P88A, Y245H). It was initially reported that RAH GrB is incapable of inducing
apoptosis, but here we show that it has essentially identical proteolytic and
cytotoxic properties to wild type GrB. Recombinant RAH and wild type GrB cleave
peptide substrates with similar kinetics, are both capable of cleaving Bid and
procaspase 3, and are equally inhibited by an endogenous regulator of GrB,
PI-9. Furthermore, cytotoxic lymphocytes from RAH heterozygotes and homozygotes
have no defect in target cell killing, and in vitro RAH GrB and wild type GrB
kill cells equally well in the presence of perforin. We conclude that the RAH
allele represents a neutral polymorphism in the GrB ge
PMID: 14752093 [PubMed - as supplied by publisher]