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Emerging Roles of TACE as a Key Protease in ErbB Ligand Shedding
Table 1.
Members of the Erbb Ligand Family Shed by Metalloproteinases
| ErbB Ligand Precursors | Ligand Binding Specificity | Candidate Metalloproteinase | Data Implicating Metalloproteinase(s) in ErbB Ligand Shedding | References |
|---|---|---|---|---|
| AR, amphiregulin; MMP, matrix metallproteinase | ||||
| aras- and myc-transformed embryonic fibroblasts | ||||
| b ADAM10 antisense strategy did not directly examine HB-EGF processing. | ||||
| cprotease-inactive. | ||||
| d NRG-1 isoforms | ||||
| Amphiregulin | ErbB1 | ADAM17/TACE | Loss of AR processing in Tace ΔZn/ΔZn fibroblastsa and restoration by TACE overexpression | (16) |
| TGFα | ErbB1 | ADAM17/TACE | Loss of TGFα processing in Tace ΔZn/ΔZn keratinocytes and restoration by TACE overexpression | (16) |
| In vitro cleavage of soluble proTGFα and TGFα peptides | ||||
| Loss of TPA-induced TGFα processing in Tace ΔZn/ΔZn fibroblastsa | (24) | |||
| Loss of TGFα processing in Tace ΔZn/ΔZn fibroblastsa | (17) | |||
| In vitro cleavage of TGFα juxtamembrane peptide | ||||
| HB-EGF | ErbB1, ErbB4 | ADAM9/Meltrinγ | Overexpression of ADAM9 and mutants in Vero cells | (44) |
| ADAM10/Kuzbanian | Antisense inhibited the lipoteichoic acid- (LTA)-induced transactivation of ErbB1 in NCIH292 cellsb | (43) | ||
| ADAM12/Meltrinα | Overexpression of ADAM12 and inactive mutantsc in HT1080 cells | (42) | ||
| ADAM17/TACE | Loss of HB-EGF processing in Tace ΔZn/ΔZn fibroblastsa and restoration by TACE overexpression | (16) | ||
| Loss of TPA-induced HB-EGF processing in Tace ΔZn/ΔZn fibroblastsa | (24) | |||
| MMP-3 | In vitro cleavage of HB-EGF-AP chimera with MMP-3 | (45) | ||
| MMP-7 | In vitro cleavage of HB-EGF with recombinant MMP-7 | (46) | ||
| Neuregulinα2cd | ErbB3, ErbB4 | ADAM17/TACE | Loss of TPA-induced NRGα2c processing in Tace ΔZn/ΔZn fibroblastsa restoration by TACE overexpression | (25) |
| Neuregulinβ1 and β4c | ErbB3, ErbB4 | ADAM19 | Overexpression of ADAM19 and inactive mutantsc | (47) |
