Active monomers of human beta-tryptase have expanded substrate specificities.
beta-Tryptase, a product of the TPSAB1 and TPSB2 genes, is a trypsin-like serine protease that is a major and selective component of the secretory granules of all human mast cells, accounting for as much as 25% of cell protein. Once mast cells are activated, beta-tryptase is released along with histamine and heparin proteoglycan. beta-Tryptase is a unique enzyme with a homotetrameric structure in which active sites face into the central cavity of the four monomers, stabilized by heparin-proteoglycan. This structure makes beta-tryptase resistant to most biological inhibitors of serine proteases. Without stabilization, at neutral pH beta-tryptase converts to inactive monomers. Tryptase levels are elevated in bronchoalveolar lavage (BAL) fluid obtained from atopic asthmatics and in serum during systemic anaphylactic shock. Several synthetic small molecular weight beta-tryptase inhibitors reduced Ag-induced airway hypersensitivity in animals, suggesting that beta-tryptase is involved in the pathogenesis of airway inflammation. Although the major biologic substrate(s) of beta-tryptase remain ambiguous, the protease can digest several proteins of potential biologic importance, including fibrinogen, fibronectin, pro-urokinase, pro-matrix metalloprotease-3 (proMMP-3), protease activated receptor-2 (PAR2) and complement component C3. Recently, monomers of beta-tryptase with enzymatic activity have been detected in vitro. Here we discuss how beta-tryptase monomers with enzymatic activity were identified as well as their potential role in vivo.
Fukuoka
Yoshihiro
Y
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0263, USA. yfukuoka@vcu.edu
Schwartz
Lawrence B
LB
D000707:Anaphylaxis / Q000097:blood / Q000201:enzymology; D001249:Asthma / Q000201:enzymology; D016535:Bronchial Hyperreactivity / Q000201:enzymology; D001991:Bronchitis / Q000201:enzymology; D015550:Cell Degranulation; D019281:Dimerization; D004789:Enzyme Activation; D004795:Enzyme Stability; D006493:Heparin / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008407:Mast Cells / Q000201:enzymology*; D008970:Molecular Weight; D020836:Protein Structure, Quaternary / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity; D053802:Tryptases / Q000737:chemistry / Q000378:metabolism*
D011509:Proteoglycans; D015842:Serine Proteinase Inhibitors; C036090:heparin proteoglycan; D006493:Heparin; D053802:Tryptases