Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.37 (
neutrophil elastase
)
4,078
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Interleukin (IL)-11 has been shown to be a crucial factor for intestinal tumorigenesis, lung carcinomas, and asthma.
IL-11
is thought to exclusively mediate its biological functions through cell-type-specific expression of the membrane-bound
IL-11
receptor (IL-11R). Here, we show that the metalloprotease ADAM10, but not ADAM17, can release the IL-11R ectodomain. Chimeric proteins of the IL-11R and the IL-6 receptor (IL-6R) revealed that a small juxtamembrane portion is responsible for this substrate specificity of ADAM17. Furthermore, we show that the serine proteases
neutrophil elastase
and proteinase 3 can also cleave the IL-11R. The resulting soluble IL-11R (sIL-11R) is biologically active and binds
IL-11
to activate cells. This
IL-11
trans-signaling pathway can be inhibited specifically by the anti-inflammatory therapeutic compound sgp130Fc. In conclusion, proteolysis of the IL-11R represents a molecular switch that controls the
IL-11
trans-signaling pathway and widens the number of cells that can be activated by
IL-11
.
...
PMID:Proteolytic Cleavage Governs Interleukin-11 Trans-signaling. 2687 77
