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Medline ® Abstract for Reference 14

of 'Laboratory tests to support the clinical diagnosis of anaphylaxis'

Promiscuous processing of human alphabeta-protryptases by cathepsins L, B, and C.
Le QT, Min HK, Xia HZ, Fukuoka Y, Katunuma N, Schwartz LB
J Immunol. 2011;186(12):7136. Epub 2011 May 11.
Humanα- andβ-protryptase zymogens are abundantly and selectively produced by mast cells, but the mechanism(s) by which they are processed is uncertain.β-Protryptase is sequentially processed in vitro by autocatalysis at R(-3) followed by cathepsin (CTS) C proteolysis to the mature enzyme. However, mast cells from CTSC-deficient mice successfully convert protryptase (pro-murine mast cell protease-6) to mature murine mast cell protease-6.α-Protryptase processing cannot occur by trypsin-like enzymes due to an R(-3)Q substitution. Thus, biological mechanisms for processing these zymogens are uncertain.β-Tryptase processing activity(ies) distinct from CTSC were partially purified from human HMC-1 cells and identified by mass spectroscopy to include CTSB and CTSL. Importantly, CTSB and CTSL also directly processα-protryptase (Q(-3)) and mutatedβ-protryptase (R(-3)Q) as well as wild-typeβ-protryptase to maturity, indicating no need for autocatalysis, unlike the CTSC pathway. Heparin promoted tryptase tetramer formation and protected tryptase from degradation by CTSB and CTSL. Thus, CTSL and CTSB are capable of directly processing bothα- andβ-protryptases from human mast cells to their mature enzymatically active products.
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.