Abstract |
SerpinB6 ( Proteinase inhibitor 6/PI-6) is an intracellular serpin produced by leukocytes, platelets, endothelial cells, keratinocytes and other epithelial cells. It is a potent cathepsin G inhibitor thought to protect monocytes, neutrophils and bystander cells from ectopic cathepsin G during inflammation. Here we show that serpinB6 also inhibits the human serine protease kallikrein-8 (hK8) and that in human and mouse skin, serpinB6 and kallikrein-8 co-localize in differentiated keratinocytes. SerpinB6 inhibits hK8 with an association rate constant (kass) of 1.8 +/- 0.2 x 10(5) M(-1)s(-1) compared to 3.4 +/- 0.2 x 10(6) M(-1) s(-1) for the interaction between the mouse orthologue of serpinB6 (SPI3/serpinb6a) and mouse kallikrein-8 (mK8). Molecular modelling suggested that the lower efficiency of the serpinB6/hK8 interaction is partly due to the bulkier P2 methionine residue of serpinB6 compared to the smaller P2 valine in SPI3. Taken together, these results suggest that serpinB6 is a physiologically relevant inhibitor of hK8 in skin. We postulate that serpinB6 protects the intracellular compartment of keratinocytes from ectopic hK8.
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Authors | Fiona L Scott, Jiuru Sun, James C Whisstock, Keiko Kato, Phillip I Bird |
Journal | Journal of biochemistry
(J Biochem)
Vol. 142
Issue 4
Pg. 435-42
(Oct 2007)
ISSN: 0021-924X [Print] England |
PMID | 17761692
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Serpins
- serpin B6
- KLK8 protein, human
- Kallikreins
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Topics |
- Animals
- Cells, Cultured
- Humans
- Intracellular Fluid
(enzymology, metabolism)
- Kallikreins
(antagonists & inhibitors, metabolism)
- Keratinocytes
(cytology, enzymology, metabolism)
- Mice
- Mice, Inbred C57BL
- Serpins
(chemistry, physiology)
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