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Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha.
Open accessAbstract
We describe here the involvement of calcium-activated neutral protease (CANP or calpain, EC 3.4.22.17) in calcium-dependent proteolytic processing of the precursor of human interleukin 1 alpha (IL-1 alpha) into mature IL-1 alpha. Calcium ionophore ionomycin enhanced proteolytic processing of pre-IL-1 alpha and the release of mature IL-1 alpha either from lipopolysaccharide (LPS)-activated human adherent mononuclear cells or from a human bladder carcinoma cell line (HTB9 5637) that constitutively produces human IL-1 alpha and -beta. The proteolytic processing of pre-IL-1 alpha was completely inhibited by EGTA. Similar calcium-dependent proteolytic processing of pre-IL-1 alpha was also observed with lysates of either LPS-activated human adherent mononuclear cells or HTB9 5637 cells. Since the optimal pH for processing was between 7 and 8, and E-64 (a cysteine protease inhibitor) and leupeptin (a serine and cysteine protease inhibitor) both inhibited this processing by cell lysates, we hypothesized that a calcium-activated neutral protease, CANP, might be responsible for this processing. This hypothesis was supported by data showing that the specific CANP inhibitor peptide inhibited this proteolysis in cell lysates in a dose-dependent fashion (IC50 = 0.05 microM) and that treatment of pre-IL-1 alpha with purified CANP yielded the 17-kDa mature form of IL-1 alpha, which has an amino terminus identical with that reported for mature human IL-1 alpha. Taken together, these findings indicate that calcium-dependent proteolytic processing of pre-IL-1 alpha is selectively mediated by CANP.
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Cited by
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Martinon, F., & Tschopp, J. (2004) · Cell · doi:10.1016/j.cell.2004.05.004 · Cited by 938
Calpain and caspase: can you tell the difference?
Wang, K. K. W. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01479-4 · Cited by 912
Nickel, W. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03577.x · Cited by 586
Interleukin 1α and the inflammatory process
Di Paolo, N. C., & Shayakhmetov, D. M. (2016) · Nature Immunology · doi:10.1038/ni.3503 · Cited by 568
Metadata
- Authors
- Kobayashi, Y., Yamamoto, K., Saido, T., Kawasaki, H., Oppenheim, J. J., & Matsushima, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1990-07
- Volume
- 87
- Issue
- 14
- Pages
- 5548-5552
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2063781137
- Cited by
- 278
- References
- 0
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. https://app.cochat.ai/papers/10.1073/pnas.87.14.5548
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- Kobayashi, Y., Yamamoto, K., Saido, T., Kawasaki, H., Oppenheim, J. J., & Matsushima, K. (1990). Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.87.14.5548
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