Mast cell tryptases and airway remodeling.
On the basis of their amino acid sequences, tryptases are just another group of serine proteinases related to trypsin that happen to be expressed and stored in mast cells rather than the pancreas. On the basis of their biochemical and biological features, however, tryptases show little family likeness to trypsin and most other trypsin-like proteases. The intriguing discrepancies have been explained by the crystal structure of the tryptase tetramer. It is now clear how tryptases, by forming tetramers, have gained the ability to prevail enzymatically active in tissues, but, at the cost of an unusual narrow substrate specificity. The tryptase tetramer thus became both a (neuro)peptidase and a long-lasting initiator that orchestrates responses by the cleavage of a few key proteins, the activation of other proteases with broader specificity, and the stimulation of cellular responses. With the support of these performers, tryptase drives a variety of processes contributing to chronic inflammation and tissue remodeling, the diversity of which is still emerging.
Sommerhoff
C P
CP
Abteilung Klinische Chemie und Klinische Biochemie, Chirurgischen Klinik Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany. sommerhoff@clinbio.med.uni-muenchen.de
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology* / Q000502:physiology* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000502:physiology; D015550:Cell Degranulation; D002908:Chronic Disease; D002918:Chymotrypsin / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology*; D008407:Mast Cells / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D010196:Pancreatic Elastase / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism / Q000502:physiology; D011480:Protease Inhibitors / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012756:Sheep; D013045:Species Specificity; D013379:Substrate Specificity; D053802:Tryptases
D018836:Inflammation Mediators; D011480:Protease Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; C509190:Tpsb2 protein, mouse; D007611:Aprotinin; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D010196:Pancreatic Elastase; C509222:Tpsab1 protein, mouse; D053802:Tryptases