Granzyme M (E7B4W) Rabbit mAb

Granzymes are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer (NK) cells and are key components of immune responses to pathogens and transformed cells (1). Granzymes are synthesized as zymogens and are processed into mature enzymes by cleavage of a leader sequence. They are released by exocytosis in lysosome-like granules containing perforin, a membrane pore-forming protein. Granzyme B has the strongest apoptotic activity of all the granzymes as a result of its caspase-like ability to cleave substrates at aspartic acid residues thereby activating procaspases directly and cleaving downstream caspase substrates (2,3).Granzyme M prefers to cleave after a Methionine or Leucine residue, and proteolyzes a restricted set of macromolecular substrates (4-7). Granzyme M is highly expressed in NK, NKT, γδ T cells, and in differentiated effector CD8+ T cells, suggesting a role for Granzyme M in both innate and adaptive immunity (4-11). After perforin-mediated entry into a target cell, various reports show Granzyme M can induce apoptosis and tumor cell death, stimulate LPS-mediated inflammation, or inhibit viral replication (4,11-15). 1.Trapani, J.A. (2001) Genome Biol. 2, REVIEWS 3014. 2.Lord, S.J. et al. (2003) Immunol. Rev. 193, 31-8. 3.Trapani, J.A. and Sutton, V.R. (2003) Curr. Opin. Immunol. 15, 533-43. 4.de Poot, S.A. and Bovenschen, N. (2014) Cell Death Differ 21, 359-68. 5.Smyth, M.J. et al. (1993) J Immunol 151, 6195-205. 6.Kelly, J.M. et al. (1996) Immunogenetics 44, 340-50. 7.Mahrus, S. et al. (2004) J Biol Chem 279, 54275-82. 8.Smyth, M.J. et al. (1995) Immunogenetics 42, 101-11. 9.de Koning, P.J. et al. (2010) Mol Immunol 47, 903-11. 10.Bade, B. et al. (2005) Int Immunol 17, 1419-28. 11.van Domselaar, R. et al. (2013) Cell Death Differ 20, 419-29. 12.Lu, H. et al. (2006) J Immunol 177, 1171-8. 13.de Poot, S.A. et al. (2014) Cell Death Differ 21, 416-26. 14.van Domselaar, R. et al. (2010) J Immunol 185, 7605-13. 15.Anthony, D.A. et al. (2010) J Immunol 185, 1794-803.