Purification of ADAM 10 from bovine spleen as a TNFα convertase

Lunn, Charles A.; Fan, Xuerong; Dalie, Barbara; Miller, Kenneth G.; Zavodny, Paul J.; Narula, Satwant K.; Lundell, Daniel

doi:10.1016/s0014-5793(96)01410-x

Cited by 127 publications

(81 citation statements)

References 13 publications

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“…Certain released molecules can be cleaved by more than one enzyme, and some enzymes can cleave more than one substrate. For example, TNF-␣ cleavage can also be mediated by ADAM10 (23), and ␣-secretase activity for ␤-amyloid precursor protein has been attributed to TACE/ADAM17 (24) and ADAM9 (25). It is not known how the protease(s) select their substrate, because consensus cleavage sites have not been identified.…”

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confidence: 99%

Role of Src Kinases in the ADAM-mediated Release of L1 Adhesion Molecule from Human Tumor Cells

Gutwein

Oleszewski

Mechtersheimer

et al. 2000

Journal of Biological Chemistry

167

156

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The ectodomain of certain transmembrane molecules can be released by proteolysis, and the solubilized antigens often exert important biological functions. We demonstrated before that the L1 adhesion molecule is shed from the cell surface. Here we show that L1 release in AR breast carcinoma cells is mediated by a member of the disintegrin metalloproteinase (ADAM) family of proteinases. Up-regulation of L1 shedding by phorbol ester or pervanadate involved distinct mechanisms. Pervanadate induced shedding and rounding-up of cells from the substrate, which was blocked by the Src kinase inhibitor PP2. Tyr phosphorylation of the L1 cytoplasmic tail and the Src kinase Fyn was observed following pervanadate treatment. Up-regulation of L1 release and activation of Fyn occurred also when cells were detached by EDTA suggesting that the regulation of L1 shedding by this pathway was linked to cell morphology and adhesion. The phorbol 12-myristate 13-acetate-induced shedding was inhibited by the protein kinase C inhibitor bisindolylmaleimide I and by PD98059, a specific inhibitor of the mitogen-activated protein kinase pathway. Soluble L1 binds to the proteoglycan neurocan and in bound form could support integrin-mediated cell adhesion and migration. We propose that the release of cell-associated adhesion molecules such as L1 may be relevant to promote cell migration.Many transmembrane proteins can undergo cleavage and release of their ectodomain into the medium (for review see Refs. 1-3). These proteins are diverse in structure and function and comprise molecules such as TNF-␣ 1 (4 -8), FasL (9), interleukin-6 receptor (10, 11), L-selectin (12-14), pro-TGF-␣, and the ␤-amyloid precursor protein (15-17). Although there is evidence for a physiological function of many released molecules, a general significance for ectodomain shedding is still disputed (2). Recently, members of the ADAM metalloproteinase family, which are membrane proteins composed of a disintegrin and metalloproteinase domain, were shown to be important in ectodomain release (for review see Refs. 3 and 18). TACE/ADAM17 mediates the membrane release of TNF-␣, Lselectin, TGF-␣ (8), and TRANCE (tumor necrosis factor-related activation-induced cytokine), a TNF family member involved in osteoclastogenesis and dendritic cell survival (19). ADAM10/Kuz has been described as an ␣-secretase for the cleavage of ␤-amyloid precursor protein (20), and ADAM9 is involved in the phorbol ester-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) (21, 22). Certain released molecules can be cleaved by more than one enzyme, and some enzymes can cleave more than one substrate. For example, TNF-␣ cleavage can also be mediated by ADAM10 (23), and ␣-secretase activity for ␤-amyloid precursor protein has been attributed to TACE/ADAM17 (24) and ADAM9 (25). It is not known how the protease(s) select their substrate, because consensus cleavage sites have not been identified. In addition to the proteolytic function, some members of the ADAM famil...

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mentioning

confidence: 99%

Role of Src Kinases in the ADAM-mediated Release of L1 Adhesion Molecule from Human Tumor Cells

Gutwein

Oleszewski

Mechtersheimer

et al. 2000

Journal of Biological Chemistry

167

156

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“…Moreover, expression of a mutant form of TACE in normal cells was shown to inhibit endogenous TACE function, indicating that the reduced TNF release in mutant T cells was due to a dominant negative effect of mutant TACE rather than the absence of other TACE-like enzymes (Solomon et al, 1999). Recent reports also implicated another ADAM family proteinase ADAM 10 as a TNF convertase (Lunn et al, 1997;Rosendahl et al, 1997). These results suggest that alternative pathways for the release of membranebound pro-TNF exist in certain types of cells.…”

Section: Introductionmentioning

confidence: 68%

Murine pro-tumor necrosis factor expressed in Saccharomyces cerevisiae HF7c localizes to membrane/particulate

Jeong

Jue²

2000

Exp Mol Med

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“…[34][35][36] Although no direct comparison between the two markers has been performed, data from the literature indicate that CD69 could be far less specific than TNFa, because a significant proportion of CD69 þ cells do not produce cytokines. 37 Although TNFa secretion pathways have been reported that are independent of TACE, 38 most TNFa molecules are produced as cytoplasmic membrane proteins that are rapidly cleaved into a soluble form by TACE. [39][40][41] The use of specific TACE inhibitors has been associated with progressive accumulation of TNFa on the surface of the cytoplasmic membrane of TNFa producing cells, allowing for their specific and unequivocal identification.…”

Section: Discussionmentioning

confidence: 99%

A new simple whole blood flow cytometry-based method for simultaneous identification of activated cells and quantitative evaluation of cytokines released during activation

Rodríguez-Caballero

García‐Montero

Bueno

et al. 2004

Laboratory Investigation

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The multiple cellular and soluble elements of the immune system respond in a coordinated way, orchestrated by cytokines, to preserve the integrity of the organism. In this study, we describe a new and unique whole blood method that, with minimal sample manipulation, allows an overall evaluation of immune responses by simultaneously measuring cell activation and cytokine secretion. The identification of cells actively secreting cytokines is based on the stabilization of tumor necrosis factor a (TNFa) at the cell surface through the use of a specific inhibitor of the TNFa-converting enzyme. This inhibitor does not affect the release of cytokines other than TNFa and makes it possible to assess, in the same measurement, the phenotype of TNFa þ -secreting cells and quantify multiple secreted cytokines by using a specific and highly sensitive flow cytometry-based bead immunoassay. Upon stimulation of normal peripheral blood samples with either phorbol 12-myristate 13 acetate (PMA) plus ionomycin or lipopolysaccharide (LPS), both the number of TNFa þ cells and the amount of secreted cytokines progressively increased, the former becoming detectable first. After stimulation for 3 h with PMA plus ionomycin, cellular responses were associated with surface TNFa expression on the majority of CD3 þ T cells and secretion of Th1-associated cytokines: interferon c, interleukin (IL)-2, and to a lesser extent IL4. In turn, stimulation with LPS induced a response mainly by inflammatory cells. After 4 h of LPS-stimulation, the majority of CD14 þ monocytes showed surface TNFa expression; in parallel, high amounts of soluble IL1b, IL6, and IL8 became detectable. Likewise, stimulation of blood samples with cytomegalovirus (CMV) lysates induced viralspecific immune responses detectable in seropositive but not seronegative volunteers; such responses were associated with the detection of increased numbers of TNFa þ monocytes, TNFa þ /CD8 þ T cells and TNFa þ /CD8 À T lymphocytes in association with an increased secretion of IFNc, IL6 and TNFa.

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Purification of ADAM 10 from bovine spleen as a TNFα convertase

Cited by 127 publications

References 13 publications

Role of Src Kinases in the ADAM-mediated Release of L1 Adhesion Molecule from Human Tumor Cells

Role of Src Kinases in the ADAM-mediated Release of L1 Adhesion Molecule from Human Tumor Cells

Murine pro-tumor necrosis factor expressed in Saccharomyces cerevisiae HF7c localizes to membrane/particulate

A new simple whole blood flow cytometry-based method for simultaneous identification of activated cells and quantitative evaluation of cytokines released during activation

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