skip to main content
Language:

Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia

Le, Quang T ; Lyons, Jonathan J ; Naranjo, Andrea N ; Olivera, Ana ; Lazarus, Robert A ; Metcalfe, Dean D ; Milner, Joshua D ; Schwartz, Lawrence B

The Journal of experimental medicine, 2019-10, Vol.216 (10), p.2348-2361 [Peer Reviewed Journal]

United States: Rockefeller University Press

Full text available

Citations Cited by
  • Title:
    Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia
  • Author: Le, Quang T ; Lyons, Jonathan J ; Naranjo, Andrea N ; Olivera, Ana ; Lazarus, Robert A ; Metcalfe, Dean D ; Milner, Joshua D ; Schwartz, Lawrence B
  • Is Part Of: The Journal of experimental medicine, 2019-10, Vol.216 (10), p.2348-2361
  • Notes: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Description: Both α-tryptase and β-tryptase are preferentially expressed by human mast cells, but the purpose of α-tryptase is enigmatic, because its tetramers lack protease activity, whereas β-tryptase tetramers are active proteases. The monogenic disorder called hereditary α-tryptasemia, due to increased α-tryptase gene copies and protein expression, presents with clinical features such as vibratory urticaria and dysautonomia. We show that heterotetramers composed of 2α- and 2β-tryptase protomers (α/β-tryptase) form naturally in individuals who express α-tryptase. α/β-Tryptase, but not homotetramer, activates protease-activated receptor-2 (PAR2), which is expressed on cell types such as smooth muscle, neurons, and endothelium. Also, only α/β-tryptase makes mast cells susceptible to vibration-triggered degranulation by cleaving the α subunit of the EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) mechanosensory receptor. Allosteric effects of α-tryptase protomers on neighboring β-tryptase protomers likely result in the novel substrate repertoire of α/β-tryptase tetramers that in turn cause some of the clinical features of hereditary α-tryptasemia and of other disorders involving mast cells.
  • Publisher: United States: Rockefeller University Press
  • Language: English
Links
Back to results list
Result  1 NextGo to Next page

  • Implemented by: ABCD-USP USP   Social Network Logos: Freepik

Searching Remote Databases, Please Wait

  • Searching for
  • inscope:(USP_VIDEOS),scope:("PRIMO"),scope:(USP_FISICO),scope:(USP_EREVISTAS),scope:(USP),scope:(USP_EBOOKS),scope:(USP_PRODUCAO),primo_central_multiple_fe
  • Show me what you have so far