The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
LEKTI Fragments Specifically Inhibit KLK5, KLK7, and KLK14 and Control Desquamation through a pH-dependent Interaction
Open accessAbstract
LEKTI is a 15-domain serine proteinase inhibitor whose defective expression underlies the severe autosomal recessive ichthyosiform skin disease, Netherton syndrome. Here, we show that LEKTI is produced as a precursor rapidly cleaved by furin, generating a variety of single or multidomain LEKTI fragments secreted in cultured keratinocytes and in the epidermis. The identity of these biological fragments (D1, D5, D6, D8–D11, and D9–D15) was inferred from biochemical analysis, using a panel of LEKTI antibodies. The functional inhibitory capacity of each fragment was tested on a panel of serine proteases. All LEKTI fragments, except D1, showed specific and differential inhibition of human kallikreins 5, 7, and 14. The strongest inhibition was observed with D8–D11, toward KLK5. Kinetics analysis revealed that this interaction is rapid and irreversible, reflecting an extremely tight binding complex. We demonstrated that pH variations govern this interaction, leading to the release of active KLK5 from the complex at acidic pH. These results identify KLK5, a key actor of the desquamation process, as the major target of LEKTI. They disclose a new mechanism of skin homeostasis by which the epidermal pH gradient allows precisely regulated KLK5 activity and corneodesmosomal cleavage in the most superficial layers of the stratum corneum.
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Cites
On the size of the active site in proteases. I. Papain
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Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome
Chavanas, S., Bodemer, C., Rochat, A., Hamel-Teillac, D., Ali, M., Irvine, A. D., Bonafé, J.-L., Wilkinson, J., Taïeb, A., Barrandon, Y., et al. (2000) · Nature Genetics · doi:10.1038/75977 · Cited by 856
Self-citationCaubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., Egelrud, T., Simon, M., & Serre, G. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22512.x · Cited by 519
Self-citationDescargues, P., Deraison, C., Bonnart, C., Kreft, M., Kishibe, M., Ishida-Yamamoto, A., Elias, P., Barrandon, Y., Zambruno, G., Sonnenberg, A., et al. (2005) · Nature Genetics · doi:10.1038/ng1493 · Cited by 383
Self-citationA Proteolytic Cascade of Kallikreins in the Stratum Corneum
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Self-citationHachem, J.-P., Man, M.-Q., Crumrine, D., Uchida, Y., Brown, B. E., Rogiers, V., Roseeuw, D., Feingold, K. R., & Elias, P. M. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23838.x · Cited by 314
Self-citationLEKTI, a Novel 15-Domain Type of Human Serine Proteinase Inhibitor
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Cited by
Briot, A., Deraison, C., Lacroix, M., Bonnart, C., Robin, A., Besson, C., Dubus, P., & Hovnanian, A. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082242 · Cited by 504
Self-citationEpidermal barrier dysfunction and cutaneous sensitization in atopic diseases
Kubo, A., Nagao, K., & Amagai, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57416 · Cited by 378
Egawa, G., & Kabashima, K. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.06.002 · Cited by 265
Lawrence, M. G., Lai, J., & Clements, J. A. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0034 · Cited by 265
TSLP Expression: Cellular Sources, Triggers, and Regulatory Mechanisms
Takai, T. (2012) · Allergology International · doi:10.2332/allergolint.11-rai-0395 · Cited by 255
Metadata
- Authors
- Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., Wagberg, F., Brattsand, M., Hachem, J. P., Leonardsson, G., & Hovnanian, A.
- Venue
- Molecular Biology of the Cell
- Published
- 2007-09
- Volume
- 18
- Issue
- 9
- Pages
- 3607-3619
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W1996417355
- Cited by
- 329
- References
- 30
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., Wagberg, F., Brattsand, M., Hachem, J. P., Leonardsson, G., & Hovnanian, A. (2007). LEKTI Fragments Specifically Inhibit KLK5, KLK7, and KLK14 and Control Desquamation through a pH-dependent Interaction. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e07-02-0124
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