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カトウ ケイコ
KATO KEIKO
加藤 啓子 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 期間 | 2007/10 |
| 名称 | SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes |
| 区分 | その他 |
| 開催場所 | OXFORD UNIV PRESS JOURNAL OF BIOCHEMISTRY |
| 発表者・共同発表者等 | Fiona L. Scott,Jiuru Sun,James C. Whisstock,Keiko Kato,Phillip I. Bird |
| 発表・展示等 | 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 (k(ass)) 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. |
| DOI | 10.1093/jb/mvm156 |