Datasheet

生物学的記述

Specificity	TACE Antibody [A22J10] detects endogenous levels of total TACE protein.
Background	TACE (TNF-α converting enzyme, ADAM17) functions as a transmembrane metalloprotease of the ADAM family that executes ectodomain shedding of diverse membrane-anchored substrates to initiate signaling cascades. The protein features a zinc-dependent catalytic domain in its extracellular portion, a transmembrane helix, and a short cytoplasmic tail that responds to stimuli-induced phosphorylation. TACE cleaves pro-TNF-α at its membrane-proximal site to release mature soluble TNF-α, which binds TNFR1/2 receptors to activate NF-κB, MAPK, and caspase pathways, driving inflammation and survival signals. Constitutive and inducible shedding of TGF-α by TACE generates soluble ligand that binds EGFR, triggering receptor dimerization, autophosphorylation at tyrosine residues, and downstream activation of PI3K/Akt, Ras/ERK, and PLCγ cascades essential for proliferation and motility. Ligand-independent Notch activation occurs through TACE-mediated S2 cleavage of Notch receptors, exposing the S2 site for γ-secretase S3 processing to release NICD, which translocates to the nucleus and forms a complex with CSL/RBPJ to activate transcription of Hes/Hey repressors that maintain stem cell self-renewal and inhibit differentiation. PKC-mediated phosphorylation of the TACE cytoplasmic tail enhances catalytic activity upon GPCR or growth factor stimulation, while TIMP3 inhibits through chelation of the catalytic zinc. Overexpression correlates with mammary tumor progression, where TACE drives autocrine EGFR activation independent of receptor mutation, promoting invasion and therapeutic resistance.

Specificity

TACE Antibody [A22J10] detects endogenous levels of total TACE protein.

Background

TACE (TNF-α converting enzyme, ADAM17) functions as a transmembrane metalloprotease of the ADAM family that executes ectodomain shedding of diverse membrane-anchored substrates to initiate signaling cascades. The protein features a zinc-dependent catalytic domain in its extracellular portion, a transmembrane helix, and a short cytoplasmic tail that responds to stimuli-induced phosphorylation. TACE cleaves pro-TNF-α at its membrane-proximal site to release mature soluble TNF-α, which binds TNFR1/2 receptors to activate NF-κB, MAPK, and caspase pathways, driving inflammation and survival signals. Constitutive and inducible shedding of TGF-α by TACE generates soluble ligand that binds EGFR, triggering receptor dimerization, autophosphorylation at tyrosine residues, and downstream activation of PI3K/Akt, Ras/ERK, and PLCγ cascades essential for proliferation and motility. Ligand-independent Notch activation occurs through TACE-mediated S2 cleavage of Notch receptors, exposing the S2 site for γ-secretase S3 processing to release NICD, which translocates to the nucleus and forms a complex with CSL/RBPJ to activate transcription of Hes/Hey repressors that maintain stem cell self-renewal and inhibit differentiation. PKC-mediated phosphorylation of the TACE cytoplasmic tail enhances catalytic activity upon GPCR or growth factor stimulation, while TIMP3 inhibits through chelation of the catalytic zinc. Overexpression correlates with mammary tumor progression, where TACE drives autocrine EGFR activation independent of receptor mutation, promoting invasion and therapeutic resistance.

使用情報

Application

WB, IP

Dilution

WB	IP
1:1000	1:50

Reactivity

Human, Mouse, Rat

Source

Rabbit Monoclonal Antibody

MW

95 kDa, 120 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/12606576/
https://pubmed.ncbi.nlm.nih.gov/17218988/

Application Data

WB

Validated by Selleck

Lane 1: HCT 116, Lane 2: Neuro-2a, Lane 3: NIH/3T3, Lane 4: C6