Adam17

Summary

Gene Symbol: Adam17
Description: a disintegrin and metallopeptidase domain 17
Alias: CD156b, Tace, disintegrin and metalloproteinase domain-containing protein 17, TNF-alpha convertase, TNF-alpha converting enzyme
Species: mouse
Products:     Adam17

Top Publications

  1. Black R, Rauch C, Kozlosky C, Peschon J, Slack J, Wolfson M, et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997;385:729-33 pubmed
    ..This enzyme (called the TNF-alpha-converting enzyme, or TACE) is a new member of the family of mammalian adamalysins (or ADAMs), for which no physiological catalytic function ..
  2. Horiuchi K, Morioka H, Takaishi H, Akiyama H, Blobel C, Toyama Y. Ectodomain shedding of FLT3 ligand is mediated by TNF-alpha converting enzyme. J Immunol. 2009;182:7408-14 pubmed publisher
    ..and that this proteolytic activity was abolished in fibroblasts lacking TNF-alpha converting enzyme (TACE) and could be rescued by reintroducing wild-type TACE in these cells...
  3. La Marca R, Cerri F, Horiuchi K, Bachi A, Feltri M, Wrabetz L, et al. TACE (ADAM17) inhibits Schwann cell myelination. Nat Neurosci. 2011;14:857-65 pubmed publisher
    Tumor necrosis factor-?-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules...
  4. Murthy A, Defamie V, Smookler D, Di Grappa M, Horiuchi K, Federici M, et al. Ectodomain shedding of EGFR ligands and TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis in mice. J Clin Invest. 2010;120:2731-44 pubmed publisher
    ..inhibitor of metalloproteinases 3 (TIMP3) controls the critical sheddase a disintegrin and metalloproteinase 17 (ADAM17) and may dictate stress signaling...
  5. Moss M, Jin S, Milla M, Bickett D, Burkhart W, Carter H, et al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997;385:733-6 pubmed
    ..a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA...
  6. Sunnarborg S, Hinkle C, Stevenson M, Russell W, Raska C, Peschon J, et al. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J Biol Chem. 2002;277:12838-45 pubmed
    We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the processing of the integral membrane precursor to soluble transforming growth factor-alpha (TGF-alpha), pro-TGF-alpha...
  7. Mezyk Kopec R, Bzowska M, Stalinska K, Chełmicki T, Podkalicki M, Jucha J, et al. Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts. Cytokine. 2009;46:309-15 pubmed publisher
    b>ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF...
  8. Bozkulak E, Weinmaster G. Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling. Mol Cell Biol. 2009;29:5679-95 pubmed publisher
    ..Although both ADAM10 and ADAM17 have been reported to cleave Notch to facilitate NICD release by gamma-secretase, the relevant ADAM has remained ..
  9. Weskamp G, Schlondorff J, Lum L, Becherer J, Kim T, Saftig P, et al. Evidence for a critical role of the tumor necrosis factor alpha convertase (TACE) in ectodomain shedding of the p75 neurotrophin receptor (p75NTR). J Biol Chem. 2004;279:4241-9 pubmed
    ..hamster ovary cells that lack functional tumor necrosis factor-alpha converting enzyme (TACE, also referred to as ADAM17) and in cells isolated from adam17-/- mice, but not in cells from adam9/12/15-/- or adam10-/- mice...

More Information

Publications63

  1. Horiuchi K, Kimura T, Miyamoto T, Miyamoto K, Akiyama H, Takaishi H, et al. Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF. J Immunol. 2009;182:2093-101 pubmed publisher
    The TNF-alpha converting enzyme (TACE/ADAM17) is involved in the proteolytic release of the ectodomain of diverse cell surface proteins with critical roles in development, immunity, and hematopoiesis...
  2. Hall K, Blobel C. Interleukin-1 stimulates ADAM17 through a mechanism independent of its cytoplasmic domain or phosphorylation at threonine 735. PLoS ONE. 2012;7:e31600 pubmed publisher
    b>ADAM17 (a disintegrin and metalloproteinase) is a membrane-anchored metalloproteinase that regulates the release of EGFR-ligands, TNF? and other membrane proteins from cells...
  3. Hikita A, Tanaka N, Yamane S, Ikeda Y, Furukawa H, Tohma S, et al. Involvement of a disintegrin and metalloproteinase 10 and 17 in shedding of tumor necrosis factor-alpha. Biochem Cell Biol. 2009;87:581-93 pubmed publisher
    ..Although a disintegrin and metalloproteinase 17 (ADAM17) is considered to be the primary sheddase for TNF-alpha, it is not known whether ADAM17 is solely responsible for ..
  4. Rozenova K, Deevska G, Karakashian A, Nikolova Karakashian M. Studies on the role of acid sphingomyelinase and ceramide in the regulation of tumor necrosis factor alpha (TNFalpha)-converting enzyme activity and TNFalpha secretion in macrophages. J Biol Chem. 2010;285:21103-13 pubmed publisher
    ..The TNFalpha-converting enzyme (TACE) catalyzes the maturation of the 26-kDa precursor (pro-TNFalpha) to an active 17-kDa form (soluble (s)TNFalpha)...
  5. Horiuchi K, Kimura T, Miyamoto T, Takaishi H, Okada Y, Toyama Y, et al. Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J Immunol. 2007;179:2686-9 pubmed
    ..The TNF-alpha converting enzyme (TACE), a disintegrin and metalloprotease 17 (ADAM17), has emerged as the best candidate TNF sheddase, but other proteinases can also release TNF...
  6. Charbonneau M, Harper K, Grondin F, Pelmus M, McDonald P, Dubois C. Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by synovial cells. J Biol Chem. 2007;282:33714-24 pubmed
    ..Because TACE/ADAM17 is the predominant protease catalyzing the release of tumor necrosis factor alpha (TNFalpha), a cytokine that ..
  7. Kawaguchi N, Horiuchi K, Becherer J, Toyama Y, Besmer P, Blobel C. Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19. J Cell Sci. 2007;120:943-52 pubmed
    ..We found that both ADAM17 and ADAM19 affect Kitl1 shedding, albeit in different ways...
  8. Maretzky T, Schulte M, Ludwig A, Rose John S, Blobel C, Hartmann D, et al. L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth. Mol Cell Biol. 2005;25:9040-53 pubmed
    ..that L1 cleavage is mediated by two distinct members of the disintegrin and metalloprotease family, ADAM10 and ADAM17. This cleavage is differently regulated and leads to the generation of a membrane bound C-terminal fragment, which ..
  9. Le Gall S, Maretzky T, Issuree P, Niu X, Reiss K, Saftig P, et al. ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J Cell Sci. 2010;123:3913-22 pubmed publisher
    ..Here, we demonstrate that the membrane-anchored metalloproteinase ADAM17, but not ADAM10, is the sheddase that rapidly responds to the physiological signaling pathways stimulated by ..
  10. Horiuchi K, Miyamoto T, Takaishi H, Hakozaki A, Kosaki N, Miyauchi Y, et al. Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. J Immunol. 2007;179:6715-24 pubmed
    ..Moreover, the stimulated shedding of mCSF-1 was abrogated in fibroblasts lacking the TNF-alpha converting enzyme (TACE, also known as a disintegrin and metalloprotease 17) and was rescued by expression of wild-type TACE in these cells,..
  11. Horiuchi K, Zhou H, Kelly K, Manova K, Blobel C. Evaluation of the contributions of ADAMs 9, 12, 15, 17, and 19 to heart development and ectodomain shedding of neuregulins beta1 and beta2. Dev Biol. 2005;283:459-71 pubmed
    ..a contribution of ADAM19 to this process, but this was only evident in the absence of the major HB-EGF sheddase, ADAM17. In addition, ADAM17 emerged as the major sheddase for neuregulins beta1 and beta2 in mouse embryonic fibroblasts...
  12. Hinkle C, Sunnarborg S, Loiselle D, Parker C, Stevenson M, Russell W, et al. Selective roles for tumor necrosis factor alpha-converting enzyme/ADAM17 in the shedding of the epidermal growth factor receptor ligand family: the juxtamembrane stalk determines cleavage efficiency. J Biol Chem. 2004;279:24179-88 pubmed
    ..Previously, we established that tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) is a physiologic transforming growth factor-alpha (TGF-alpha) sheddase, and we also demonstrated enhanced ..
  13. Bell J, Herrera A, Li Y, Walcheck B. Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages. J Leukoc Biol. 2007;82:173-6 pubmed
    ..The role of a disintegrin and metalloproteinase 17 (ADAM17) in this process by the major professional phagocytes neutrophils and macrophages, the primary producers of TNF-..
  14. Chalaris A, Rabe B, Paliga K, Lange H, Laskay T, Fielding C, et al. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood. 2007;110:1748-55 pubmed
    ..Apoptosis-induced shedding of the IL6R was caspase dependent but PKC independent, with inhibition of ADAM17 preventing IL6R shedding...
  15. Soond S, Everson B, Riches D, Murphy G. ERK-mediated phosphorylation of Thr735 in TNFalpha-converting enzyme and its potential role in TACE protein trafficking. J Cell Sci. 2005;118:2371-80 pubmed
    Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) has been implicated in the inducible shedding of numerous cell surface proteins...
  16. Lee D, Sunnarborg S, Hinkle C, Myers T, Stevenson M, Russell W, et al. TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann N Y Acad Sci. 2003;995:22-38 pubmed
    ..We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane precursor, proTGFalpha...
  17. Zhao J, Chen H, Peschon J, Shi W, Zhang Y, Frank S, et al. Pulmonary hypoplasia in mice lacking tumor necrosis factor-alpha converting enzyme indicates an indispensable role for cell surface protein shedding during embryonic lung branching morphogenesis. Dev Biol. 2001;232:204-18 pubmed
    ..The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE/ADAM-17), is a transmembrane metalloprotease-disintegrin that cleaves multiple cell surface proteins, although it ..
  18. Zhou H, Weskamp G, Chesneau V, Sahin U, Vortkamp A, Horiuchi K, et al. Essential role for ADAM19 in cardiovascular morphogenesis. Mol Cell Biol. 2004;24:96-104 pubmed
    ..Most adam19(-/-) animals die perinatally, likely as a result of their cardiac defects. These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects. ..
  19. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science. 2012;335:225-8 pubmed publisher
    ..the active signal is its ectodomain, which is shed from cells after cleavage by an ADAM family metalloprotease, ADAM17 (TNF?-converting enzyme, TACE)...
  20. Kim M, Zhang B, Mills I, Milla M, Brunden K, Lee V. Effects of TNFalpha-converting enzyme inhibition on amyloid beta production and APP processing in vitro and in vivo. J Neurosci. 2008;28:12052-61 pubmed publisher
    ..Because TNFalpha is released from cell membranes by the TNFalpha-converting enzyme (TACE), inhibition of TACE has the potential to mitigate TNFalpha effects in AD brain...
  21. Sahin U, Weskamp G, Kelly K, Zhou H, Higashiyama S, Peschon J, et al. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol. 2004;164:769-79 pubmed
    ..ADAM10 emerged as the main sheddase of EGF and betacellulin, and ADAM17 as the major convertase of epiregulin, transforming growth factor alpha, amphiregulin, and heparin-binding EGF-..
  22. Amour A, Slocombe P, Webster A, Butler M, Knight C, Smith B, et al. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Lett. 1998;435:39-44 pubmed
    TNF-alpha converting enzyme (TACE; ADAM-17) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to a soluble form...
  23. Li Y, Brazzell J, Herrera A, Walcheck B. ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding. Blood. 2006;108:2275-9 pubmed
    ..Tumor necrosis factor-alpha-converting enzyme (TACE, or ADAM17) is a sheddase of L-selectin; however, Adam17 gene targeting (ADAM17(DeltaZn/DeltaZn)) in mice is perinatal lethal ..
  24. Sahin U, Blobel C. Ectodomain shedding of the EGF-receptor ligand epigen is mediated by ADAM17. FEBS Lett. 2007;581:41-4 pubmed
    ..Here we show that ectodomain shedding of epigen requires ADAM17, which can be stimulated by phorbol esters, phosphatase inhibitors and calcium influx...
  25. Peschon J, Slack J, Reddy P, Stocking K, Sunnarborg S, Lee D, et al. An essential role for ectodomain shedding in mammalian development. Science. 1998;282:1281-4 pubmed
    ..The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released...
  26. Maretzky T, Evers A, Zhou W, Swendeman S, Wong P, Rafii S, et al. Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17. Nat Commun. 2011;2:229 pubmed publisher
    ..signalling and cell migration in epithelial cells require stimulation of the membrane-anchored metalloproteinase ADAM17 and release of heparin-binding epidermal growth factor (HB-EGF)...
  27. Zhao X, Oliver P, Song K, Schurr J, Zhang Z, Kolls J. Chronic ethanol enhances ectodomain shedding in T cells and monocytes. Alcohol Clin Exp Res. 2004;28:1399-407 pubmed
    ..with increased levels of TNF messenger RNA (mRNA) as well as increased processing of TNF by TNF converting enzyme (TACE), the enzymatic activity of which is regulated by the cellular redox state...
  28. Murthy A, Shao Y, Narala S, Molyneux S, Zuniga Pflucker J, Khokha R. Notch activation by the metalloproteinase ADAM17 regulates myeloproliferation and atopic barrier immunity by suppressing epithelial cytokine synthesis. Immunity. 2012;36:105-19 pubmed publisher
    ..Here we have shown that keratinocyte-specific deletion of a disintegrin and metalloproteinase 17 (Adam17) triggers T helper 2 and/or T helper 17 (Th2 and/or Th17) cell-driven atopic dermatitis and myeloproliferative ..
  29. Jackson L, Qiu T, Sunnarborg S, Chang A, Zhang C, Patterson C, et al. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J. 2003;22:2704-16 pubmed
    ..valvulogenesis was observed in newborn mice lacking EGFR and tumor necrosis factor-alpha converting enzyme (TACE)...
  30. Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann Koch J, Schirmacher P, et al. Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice. J Exp Med. 2010;207:1617-24 pubmed publisher
    ..b>ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer...
  31. Weskamp G, Mendelson K, Swendeman S, Le Gall S, Ma Y, Lyman S, et al. Pathological neovascularization is reduced by inactivation of ADAM17 in endothelial cells but not in pericytes. Circ Res. 2010;106:932-40 pubmed publisher
    ..studies showed that vascular endothelial growth factor (VEGF)-A activates the membrane-anchored metalloproteinase ADAM17 (a disintegrin and metalloproteinase 17) in endothelial cells, thereby stimulating crosstalk between VEGF receptor ..
  32. Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens J, et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell. 2000;5:207-16 pubmed
    ..Purification of the activity accounting for this cleavage in vitro shows that it is due to TACE (TNFalpha-converting enzyme), a member of the ADAM (a disintegrin and metalloprotease domain) family of ..
  33. Swendeman S, Mendelson K, Weskamp G, Horiuchi K, Deutsch U, Scherle P, et al. VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling. Circ Res. 2008;103:916-8 pubmed publisher
    ..Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10...
  34. Gelling R, Yan W, Al Noori S, Pardini A, Morton G, Ogimoto K, et al. Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice. Endocrinology. 2008;149:6053-64 pubmed publisher
    ..Here, we report that adult homozygous TNFalpha converting enzyme (TACE)-deficient mice exhibit one of the most dramatic examples of hypermetabolism yet reported in a rodent system...
  35. Franzke C, Bruckner Tuderman L, Blobel C. Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9. J Biol Chem. 2009;284:23386-96 pubmed publisher
    ..Previous studies identified ADAMs 9, 10, and 17 as candidate collagen XVII sheddases and suggested that ADAM17 is a major sheddase...
  36. Black R. Tumor necrosis factor-alpha converting enzyme. Int J Biochem Cell Biol. 2002;34:1-5 pubmed
    Tumor necrosis factor-alpha converting enzyme (TACE/ADAM17/CD156q) is a member of the 'A Disintegrin And Metalloprotease', or ADAM, family...
  37. Koenen R, Pruessmeyer J, Soehnlein O, Fraemohs L, Zernecke A, Schwarz N, et al. Regulated release and functional modulation of junctional adhesion molecule A by disintegrin metalloproteinases. Blood. 2009;113:4799-809 pubmed publisher
    ..Therefore, shedding of JAM-A by inflamed vascular endothelium via ADAM17 and ADAM10 may not only generate a biomarker for vascular inflammation but could also be instrumental in ..
  38. Garbers C, Jänner N, Chalaris A, Moss M, Floss D, Meyer D, et al. Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding. J Biol Chem. 2011;286:14804-11 pubmed publisher
    Hypomorphic ADAM17(ex/ex) mice showed defects in mucosal regeneration due to inefficient enhanced GFR shedding. ADAM17 is the main sheddase of interleukin-6 receptor (IL-6R) to induce IL-6 trans-signaling...
  39. Yang Y, Jalal F, Thompson J, Walker E, Candelario Jalil E, Li L, et al. Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-?/TACE in focal cerebral ischemia in mice. J Neuroinflammation. 2011;8:108 pubmed publisher
    ..b>TACE activity was significantly increased in ischemic WT white matter, which was expressed in active microglia/..
  40. Wang S, Xiang B, Guix M, Olivares M, Parker J, Chung C, et al. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol Cell Biol. 2008;28:5605-20 pubmed publisher
    ..an activated TGF-beta type I receptor (Alk5 with the mutation T204D [Alk5(T204D)]) induced phosphorylation of TACE/ADAM17 and its translocation to the cell surface, resulting in increased secretion of TGF-alpha, amphiregulin, and ..
  41. Arndt P, Strahan B, Wang Y, Long C, Horiuchi K, Walcheck B. Leukocyte ADAM17 regulates acute pulmonary inflammation. PLoS ONE. 2011;6:e19938 pubmed publisher
    The transmembrane protease ADAM17 regulates the release and density of various leukocyte cell surface proteins that modulate inflammation, including L-selectin, TNF-?, and IL-6R...
  42. Bergmeier W, Piffath C, Cheng G, Dole V, Zhang Y, von Andrian U, et al. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res. 2004;95:677-83 pubmed
    ..in platelets obtained from chimeric mice, which express inactive tumor necrosis factor-alpha converting enzyme (TACE(DeltaZn/DeltaZn)) in blood cells only...
  43. Reddy P, Slack J, Davis R, Cerretti D, Kozlosky C, Blanton R, et al. Functional analysis of the domain structure of tumor necrosis factor-alpha converting enzyme. J Biol Chem. 2000;275:14608-14 pubmed
    ..The tumor necrosis factor (TNF)-alpha converting enzyme (TACE/ADAM-17) is a transmembrane metalloproteinase responsible for the proteolytic release or "shedding" of ..
  44. Schlondorff J, Blobel C. Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci. 1999;112 ( Pt 21):3603-17 pubmed
  45. Cerretti D, Poindexter K, Castner B, Means G, Copeland N, Gilbert D, et al. Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25. Cytokine. 1999;11:541-51 pubmed
    ..Recently, a human protease responsible for this shedding, the TNF-alpha converting enzyme (TACE/ADAM17), was isolated...
  46. Shi W, Chen H, Sun J, Buckley S, Zhao J, Anderson K, et al. TACE is required for fetal murine cardiac development and modeling. Dev Biol. 2003;261:371-80 pubmed
    Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-anchored, Zn-dependent metalloprotease, which belongs to the ADAM (a disintegrin and metalloprotease) family...
  47. Horiuchi K, Le Gall S, Schulte M, Yamaguchi T, Reiss K, Murphy G, et al. Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx. Mol Biol Cell. 2007;18:176-88 pubmed
    ..Phorbol esters predominantly activate ADAM17, thereby triggering a burst of shedding of EGFR-ligands from a late secretory pathway compartment...
  48. Sternlicht M, Sunnarborg S, Kouros Mehr H, Yu Y, Lee D, Werb Z. Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Development. 2005;132:3923-33 pubmed
    ..As the transmembrane metalloproteinase ADAM17 can process AREG in culture and Adam17(-/-) mice tend to phenocopy Egfr(-/-) mice, we examined the role of each of ..
  49. Long C, Wang Y, Herrera A, Horiuchi K, Walcheck B. In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E. coli-mediated peritonitis. J Leukoc Biol. 2010;87:1097-101 pubmed publisher
    ..Ectodomain shedding by the membrane metalloprotease ADAM17 is an emerging regulator of inflammation, as it directs the activity of various inflammatory modulators...
  50. Lemjabbar H, Li D, Gallup M, Sidhu S, Drori E, Basbaum C. Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor alpha-converting enzyme and amphiregulin. J Biol Chem. 2003;278:26202-7 pubmed
    ..These results shed light on the pathogenesis of lung cancer, suggest novel drug targets for the reduction of cancer risk in smokers, and provide insight into how EGFR integrates responses to diverse noxious stimuli. ..
  51. McIlwain D, Lang P, Maretzky T, Hamada K, Ohishi K, Maney S, et al. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science. 2012;335:229-32 pubmed publisher
    ..is tumor necrosis factor-? (TNF?), which is shed from the plasma membrane after cleavage by the TNF? convertase (TACE). We report that the rhomboid family member iRhom2 interacted with TACE and regulated TNF? shedding...
  52. Li N, Boyd K, Dempsey P, Vignali D. Non-cell autonomous expression of TNF-alpha-converting enzyme ADAM17 is required for normal lymphocyte development. J Immunol. 2007;178:4214-21 pubmed
    TNF-alpha converting enzyme (TACE; ADAM17), a member of the ADAM (a disintegrin and metalloprotease) family of metalloproteases, has been shown to cleave a wide variety of cell surface proteins of immunological importance...
  53. Mishra H, Johnson T, Seelig D, Walcheck B. Targeting ADAM17 in leukocytes increases neutrophil recruitment and reduces bacterial spread during polymicrobial sepsis. J Leukoc Biol. 2016;100:999-1004 pubmed
    ..Taken together, our findings suggest that extensive a disintegrin and metalloprotease-17 induction during sepsis may tip the balance between efficient and impaired neutrophil recruitment. ..
  54. Capone C, Dabertrand F, Baron Menguy C, Chalaris A, Ghezali L, Domenga Denier V, et al. Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics. elife. 2016;5: pubmed publisher
    ..Here, we show that TIMP3 acts through inhibition of the metalloprotease ADAM17 and HB-EGF to regulate cerebral arterial tone and blood flow responses...