3.4.24.81: ADAM10 endopeptidase
This is an abbreviated version!
For detailed information about ADAM10 endopeptidase, go to the full flat file.
Word Map on EC 3.4.24.81
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3.4.24.81
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alzheimer
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adam17
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amyloid
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ectodomain
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sheddase
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alpha-secretase
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endothelial
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metalloproteases
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neuroprotective
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plaque
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amyloidogenic
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non-amyloidogenic
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tnf
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sh-sy5y
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synaptic
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secretase
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membrane-anchored
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tetraspanins
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gamma-secretase
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n-cadherin
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presenilins
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notch1
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intramembrane
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abeta
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cxcl16
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prpc
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prion
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amyloid-beta
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prodomains
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psen1
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beta-secretase
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sappalpha
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hb-egf
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beta-site
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trans-signaling
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amphiregulin
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fractalkine
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meprin
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disintegrin-like
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adam17-mediated
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app-cleaving
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betacellulin
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nicastrin
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timp-3
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molecular biology
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anti-amyloidogenic
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medicine
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srage
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notch-dependent
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ad-like
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juxtamembrane
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bace-1
- 3.4.24.81
- alzheimer
- adam17
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amyloid
- ectodomain
- sheddase
- alpha-secretase
- endothelial
- metalloproteases
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neuroprotective
- plaque
-
amyloidogenic
-
non-amyloidogenic
- tnf
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sh-sy5y
- synaptic
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secretase
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membrane-anchored
- tetraspanins
- gamma-secretase
- n-cadherin
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presenilins
- notch1
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intramembrane
- abeta
- cxcl16
- prpc
- prion
- amyloid-beta
- prodomains
- psen1
- beta-secretase
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sappalpha
- hb-egf
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beta-site
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trans-signaling
- amphiregulin
- fractalkine
- meprin
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disintegrin-like
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adam17-mediated
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app-cleaving
- betacellulin
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nicastrin
- timp-3
- molecular biology
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anti-amyloidogenic
- medicine
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srage
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notch-dependent
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ad-like
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juxtamembrane
- bace-1
Reaction
endopeptidase of broad specificity =
Synonyms
a disintegrin and metalloprotease 10, a disintegrin and metalloproteinase 10, a disintegrin and metalloproteinase-10, a-disintegrin-and-metalloprotease 10, AD10, ADAM 10, ADAM-10, ADAM10, CD156c, CD23 metalloprotease, HsT18717, kuz, kuzbanian, Kuzbanian protein, MADM, mammalian disintegrin-metalloprotease, metalloproteinase 10, metalloproteinase ADAM10, metalloproteinase Kuzbanian, metalloproteinase MADM, metalloproteinase-disintegrin, myelin-associated disintegrin metalloproteinase, notch proteinase, transmembrane metzinkin-protease of the a disintegrin and metalloproteinase family-10
ECTree
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General Information
General Information on EC 3.4.24.81 - ADAM10 endopeptidase
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malfunction
metabolism
physiological function
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Adam10-/- mice die at embryonic day 9.5, due to major defects in development of somites and vasculogenesis. Generation of Adam10 conditional knock-out (cKO) mice using a Nestin-Cre promotor, limiting ADAM10 inactivation to neural progenitor cells (NPCs) and NPC-derived neurons and glial cells. The cKO mice die perinatally with a disrupted neocortex and a severely reduced ganglionic eminence, due to precocious neuronal differentiation resulting in an early depletion of progenitor cells. Premature neuronal differentiation is associated with aberrant neuronal migration and a disorganized laminar architecture in the neocortex. Neurospheres derived from Adam10 cKO mice have a disrupted sphere organization and segregated more neurons at the expense of astrocytes. Notch-1 processing is affected, leading to downregulation of several Notch-regulated genes in Adam10
malfunction
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knockdown of both endogenous ADAM10 and endogenous ADAM17 inhibits FcalphaR shedding, demonstrating that ADAM10 and ADAM17 are involved in the shedding of FcalphaR
malfunction
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mice with a dominant negative mutant of ADAM10 show lowered amounts of APPs-alpha, accompanied by an enhanced amount of plaques and learning deficiencies in the Morris water maze test
malfunction
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to determine the involvement of ADAM10 and ADAM17 in G protein coupled receptor P2Y2 nucleotide receptor-mediated EGFR activation, human salivary gland cells are transfected with small interfering RNA targeting either ADAM10 or ADAM17 mRNA. Transfection of human salivary gland cells with ADAM10 or ADAM17 siRNA partially suppress EGFR and ERK1/2 phosphorylation induced by UTP, whereas co-transfection with both ADAM10 and ADAM17 siRNA almost completely preventd UTP-induced EGFR and ERK1/2 phosphorylation
malfunction
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ADAM10 deletion causes reduced Notch signaling in vivo. Adam10-deficient mice die at embryonic day 9.5, due to major defects in development of somites and vasculogenesis. Adam10 conditional knock-out mice die perinatally with a disrupted neocortex and a severely reduced ganglionic eminence, due to precocious neuronal differentiation resulting in an early depletion of progenitor cells
malfunction
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B-cell specific ADAM10 deficient mice have severely diminished primary and secondary responses after T-dependent immunization, display impaired germinal center formation, have fewer follicular T helper cells, decreased follicular dendritic cell networks, and altered chemokine expression in draining lymph nodes
malfunction
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deletion of ADAM10 prevents development of the entire marginal zone B cell lineage
malfunction
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inhibition of ADAM10 activity in the intestine of mice results in a lack of compartmentalization of Paneth cells within the crypt stem cell niche
malfunction
enzyme depletion in forebrain neurons leads to posttranslational increase of cellular prion protein levels
malfunction
enzyme inhibition selectively increases glioma sphere-forming cell, but not neural stem cell, migration out of tumourspheres towards fibronectin
malfunction
enzyme knockdown inhibits the CNE-2 nasopharyngeal carcinoma cell proliferation and migration
malfunction
enzyme knockout in cranial neural crest cells leads to embryonic death, craniofacial dysmorphia and bone defects
malfunction
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enzyme-deficient embryos die at E 9.5 due to developmental defects in somitogenesis, neurogenesis and vasculogenesis
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ADAM10 as a major alpha-secretase in the ectodomain shedding of nectin-1
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ADAM10 and ADAM17 are activated by G protein-coupled receptor P2Y2
physiological function
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ADAM10 and TACE (EC 3.4.24.86) are the major sheddases that balance the beta-site amyloid precursor protein cleaving enzyme-driven generation of Abeta peptides
physiological function
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ADAM10 and TACE (EC 3.4.24.86) are the major sheddases that balance the beta-site amyloid precursor protein cleaving enzyme-driven generation of Abeta peptides. ADAM10 regulates axon withdrawal by ephrin. ADAM10 plays a role in the aetiology of Alzheimers disease
physiological function
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ADAM10 cleaves ephrin from its membrane tether on the opposite cell (through its so-called sheddase activity), thereby separating the cell-cell connection and allowing the signalling complex to internalise. Ephrin-A5 shedding by ADAM10 is controlled by steric hindrance exerted by the membrane-proximal EphA3 kinase domain, which prevents the functional interaction with ADAM10 that is needed for efficient substrate (ephrin) cleavage to occur
physiological function
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ADAM10 has no direct influence on PrPc proteolytic processing in vivo. Overexpression of active ADAM10 in transgenic mice leads to a reduced amount of PrP mRNA
physiological function
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ADAM10 is a major TNF sheddase in ADAM17-deficient fibroblasts. TNF is a major pro-inflammatory cytokine with broad immune effects
physiological function
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ADAM10 is a primary enzymes responsible for catalysing release of membrane-anchored proteins from the cell surface in metazoan organisms
physiological function
ADAM10 is involved in the proteolytic processing and shedding of proteins such as the amyloid precursor protein, cadherins, and the Notch receptors, thereby initiating the regulated intramembrane proteolysis of these proteins. ADAM10 performs a dual role in cells, as a metalloprotease when it is membrane-bound, and as a potential signaling protein once cleaved by ADAM9/15 and the alpha-secretase
physiological function
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ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including amyloid precursor protein
physiological function
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ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha
physiological function
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although Notch1 is a substrate for both ADAM10 and ADAM17, the particular ADAM required for receptor activation is context dependent. Specifically, ADAM10 is absolutely required for Notch1 signaling induced by ligands. Noth proteases participated in signaling intrinsic to Notch1 mutations associated with leukemia
physiological function
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expression of ADAM 10 in dermal papilla cells may imply a role in the induction and development of anagen hair follicles. Expression of ADAM 10 in the outer root sheath and hair bulb assume the involvment of ADAM 10 in the downward migration of anagen hair follicles
physiological function
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human mesenchymal stem cells interfere with cellcell adhesion and enhance migration of breast cancer cells by activating ADAM10
physiological function
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regulated proteolytic processing by ADAM10 and PS/gamma-secretase is essential for the nuclear signalling of L1
physiological function
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the enzyme is responsible for the ectodomain shedding of a number of proteins implicated in the pathogenesis of diseases ranging from cancer to Alzheimer's disease
physiological function
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ADAM10 activity is required for insulin-like growth factor-1-induced secretion of soluble amyloid-beta precurso protein
physiological function
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ADAM10 represents the most important amyloid precursor protein alpha-secretase in brain. ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including amyloid precursor protein
physiological function
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ADAM10 activity acts continuously at sites of EphB-ephrin-B interaction to prevent the formation of E-cadherin-mediated cell adhesion. ADAM10 metalloproteinase activity is required for EphB/ephrin-B-mediated cell sorting and E-cadherin remodelling
physiological function
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ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. ADAM10 initiates Notch2 signaling
physiological function
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ADAM10 is essential for the maintenance of lymphoid structure after antigen challenge
physiological function
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ADAM10 localization and activity at synapse regulate excitatory synapses through N-cadherin cleavage, influence spine morphology, subunit composition and function of synaptic AMPA receptors
physiological function
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annexin A1 proteolytic processing by ADAM10 into a chemotactic peptide represents a final events during apoptosis, which after the transition to secondary necrosis contributes to the recruitment of monocytes and the prevention of inflammation
physiological function
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Adam10 deficiency in ureteric bud derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis. Adam10 deficiency leads to a reduction in the percentage of aquaporin 2+ principal cells in the collecting ducts that is accompanied by a proportional increase in the percentage of intercalated cells. Foxi1, a transcription factor important for the differentiation of intercalated cells, is upregulated in the Adam10 mutants
physiological function
ADAM10 is the major ADAM metalloproteinase responsible for the constitutive and stimulated shedding of meprin beta and meprin A
physiological function
collagen binding induces ADAM10-dependent ectodomain shedding of discoidin domain receptor DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling are shed in an efficient manner. DDR1 and ADAM10 are in a complex on the cell surface, but shedding does not occur unless collagen binds to DDR1. ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor
physiological function
endopeptidase ADAM10 selectively regulates Notch receptors and ligands in en dothelial cells and promotes Dll4 expression. ADAM10 mediates a canonical Notch dependent release of interleukin IL-6, dependent of gamma-secretase activity. The production of IL-6 through ADAM10/Notch signaling in endothelial cells requires the involvement of the phosphoinositol 3-kinase pathway
physiological function
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loss of ADAM10 from developing and adult intestine causes lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion leads to the replacement of intestinal cell progenitors with post-mitotic, secretory cell lineages: intermediate-like and enteroendocrine cells. ADAM10 controls these cell fate decisions by regulating Notch signaling. ADAM10 is required for survival of Lgr5+ crypt-based columnar cells
physiological function
overexpression of ADAM10 and ADAM17 increase cleavage of cell surface VEGF receptor Flt while knockdown of ADAM10 and ADAM17 reduce N-terminal cleavage suggesting that these metalloproteases are responsible for Flt1 cleavage
physiological function
Staphylococcus aureus alpha-hemolysin, a pore-forming cytotoxin, is required for full virulence in a murine sepsis model. The alpha-hemolysin binding to its receptor A-disintegrin and metalloprotease ADAM10 upregulates the receptor's metalloprotease activity on endothelial cells, causing vascular endothelial-cadherin cleavage and concomitant loss of endothelial barrier function
physiological function
upon deletion of ADAM10 in B cells, antibody responses are impaired despite normal germinal center formation in mice, implicating ADAM10 in post-germinal center and extrafollicular B cell terminal differentiation. Plasma cell numbers are normal in ADAM10 deletion mice when compared to controls. Plasma cells of the deletion strain exhibit decreased expression of transcription factors important for their function: Prdm1, Xbp1 and Irf4. Transcriptional repressor Bcl6 expression is increased in plasma cells isolated from ADAM10 deletion mice at both the mRNA and protein level
physiological function
enzyme overexpression promotes the progression and migration of nasopharyngeal carcinoma
physiological function
interaction of Cry3Aa toxin with ADAM10 metalloprotease is an essential part of the mode of action of this toxin. ADAM10 is a Cry3Aa toxin functional receptor
physiological function
the enzyme critically contributes to alpha-toxin-dependent pathology of experimental Staphylococcus aureus infections in mice
physiological function
the enzyme has deleterious effects for patients with brain tumors because it may promote the spreading of tumor cells. The level and/or activity of ADAM10 affects neuronal structures in the adult brain, in particular dendritic spines
physiological function
the enzyme is directly involved in the development of Alzheimer's disease, prion diseases, fragile X syndrome and possibly Huntington disease
physiological function
the enzyme is essential for cranial neural crest-derived maxillofacial bone development
physiological function
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the enzyme is essential for intestinal development. Several signaling pathways that undergo ectodomain shedding by the enzyme (e.g. Notch, EGFR/ErbB, interleukin-6/sinterleukin-6R) help control intestinal injury/regenerative responses and may drive intestinal inflammation and colon cancer initiation and progression. The enzyme is associated with regulated intramembrane proteolysis activity
physiological function
the enzyme mediates a canonical Notch-dependent regulation of IL-6 through Dll4 in human endothelial cells. ADAM10/Dll4 signaling is a major signaling pathway in endothelial cells driving inflammatory events involved in inflammation and immune cell recruitment
physiological function
the enzyme promotes binding of alpha-toxin to human keratinocytes. The enzyme is required but insufficient to sensitize cells to alpha-toxin. The enzyme does not sensitize cells to Vibrio cholerae cytolysin