Jun 26, 2024 · ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8 + T cells. Intriguingly, inhibition of ADAM17 in CD8 + T cells...

ADAM17 may play a prominent role in the Notch signaling pathway, during the proteolytic release of the Notch intracellular domain (from the Notch1 receptor) that occurs following ligand binding. ADAM17 also regulates the MAP kinase signaling pathway by regulating shedding of the EGFR ligand amphiregulin in the mammary gland. [11] .

ADAM17 activation orchestrates three major signal transduction pathways, namely IL-6 trans-signaling, stimulation of the TNFα signaling pathway via TNF-R I and the EGF-R pathway via cleavage of EGF-R ligands such as amphiregulin, TGFα, or Hb-EGF.

Jan 1, 2022 · ADAM17 plays an important role in the biology of Interleukin-6 (IL-6) since the generation of the soluble Interleukin-6 receptor (sIL-6R) is needed for trans-signaling, which has been identified as the pro-inflammatory activity of this cytokine.

ADAM17 inhibitors have broad therapeutic potential, with properties ranging from tumor immunosurveillance and overcoming drug and radiation resistance in cancer, as treatments for cardiac hypertrophy and inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis.

A recent study demonstrated that ADAM17 regulates TGF-β-mediated EMT through the cleavage of vasorin (VSN), a type I transmembrane protein initially identified in screening to isolate novel proteins containing a signal sequence.

Jul 13, 2011 · ADAM17 modulates inflammation by activation of TNFR- and IL-6R-mediated signal transduction. Therefore, ADAM17 activation is considered a pro-inflammatory event.

Jun 26, 2024 · T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8 + T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8 + T cells through cleavage of membrane CD122.

Oct 12, 2016 · We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the...

Nov 13, 2024 · ADAM17, through trans-signaling, cleaves the membrane interleukin-6 receptor (mIL-6R) to free a soluble molecule, which then associates with free IL-6 to constitute a signal-transducing receptor complex with gp130 and induce its dimerization.