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
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