title: Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6.
abstract: Kallikrein-related peptidases (KLKs) are a group of serine proteases, expressed in several tissues. Their activity is regulated by inhibitors including members of the serine protease of Kazal-type (SPINK) family. Recently, we discovered that SPINK6 is expressed in human skin and inhibits KLK5, KLK7, KLK14 but not KLK8. In this study we tested whether SPINK6 inhibits other members of the KLK family and caspase-14. Using chromogenic substrates, SPINK6 exhibited inhibitory activity against KLK12 and KLK13 with K(i) around 1nM, KLK4 with K(i)=27.3nM, KLK6 with K(i)=140nM, caspase-14 with a K(i) approximating 1μM and no activity against KLK1, KLK3 and KLK11. Taken together, SPINK6 is a potent inhibitor of distinct KLKs members.
authors: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, D-24105 Kiel, Germany.
authors: Tomasz
authors: T
authors: Kantyka
authors: Jan
authors: J
authors: Fischer
authors: Zhihong
authors: Z
authors: Wu
authors: Wim
authors: W
authors: Declercq
authors: Karina
authors: K
authors: Reiss
authors: Jens-Michael
authors: JM
authors: Schröder
authors: Ulf
authors: U
authors: Meyer-Hoffert
mesh_terms: D000595:Amino Acid Sequence; D053456:Caspase 14 / Q000378:metabolism; D061945:Caspase Inhibitors; D002863:Chromogenic Compounds / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012996:Solutions; D013053:Spectrophotometry; D013379:Substrate Specificity
chemical_list: D061945:Caspase Inhibitors; D002863:Chromogenic Compounds; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins; C553928:SPINK6 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors; D012996:Solutions; D007610:Kallikreins; D053456:Caspase 14