A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation

被引:215
作者
Borgono, Carla A.
Michael, Iacovos P.
Komatsu, Nahoko
Jayakumar, Arumugam
Kapadia, Ravi
Clayman, Gary L.
Sotiropoulou, Georgia
Diamandis, Eleftherios P.
机构
[1] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada
[3] Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA
[4] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[5] Univ Patras, Sch Hlth Sci, Dept Pharm, Patras 26500, Greece
关键词
D O I
10.1074/jbc.M607567200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Desquamation of the stratum corneum is a serine protease-dependent process. Two members of the human tissue kallikrein (KLK) family of (chymo)tryptic-like serine proteases, KLK5 and KLK7, are implicated in desquamation by digestion of (corneo)desmosomes and inhibition by desquamation-related serine protease inhibitors (SPIs). However, the epidermal localization and specificity of additional KLKs also supports a role for these enzymes in desquamation. This study aims to delineate the probable contribution of KLK1, KLK5, KLK6, KLK13, and KLK14 to desquamation by examining their interactions, in vitro, with: 1) colocalized SPI, lympho-epithelial Kazal-type-related inhibitor (LEKTI, four recombinant fragments containing inhibitory domains 1-6 (rLEKTI(1-6)), domains 6-8 and partial domain 9 (rLEKTI(6 -9')), domains 9-12 (rLEKTI(9-12)), and domains 12-15 (rLEKTI(12-15)), secretory leukocyte protease inhibitor, and elafin and 2) their ability to digest the (corneo)desmosomal cadherin, desmoglein 1.KLK1 was not inhibited by any SPI tested. KLK5, KLK6, KLK13, and KLK14 were potently inhibited by rLEKTI(1-6), rLEKTI(6-9'), and rLEKTI(9-12) with K-i values in the range of 2.3-28.4 nM, 6.1-221 nM, and 2.7-416 nM for each respective fragment. Only KLK5 was inhibited by rLEKTI(12-15) (K-i = 21.8 nM). No KLK was inhibited by secretory leukocyte protease inhibitor or elafin. Apart from KLK13, all KLKs digested the ectodomain of desmoglein 1 within cadherin repeats, Ca2+ binding sites, or in the juxtamembrane region. Our study indicates that multiple KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI. These findings may have clinical implications for the treatment of skin disorders in which KLK activity is elevated.
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页码:3640 / 3652
页数:13
相关论文
共 84 条
[1]   Purification and partial amino acid sequence of proteins from human epidermal keratinocyte conditioned medium [J].
Ahmed, A ;
Kandola, P ;
Ziada, G ;
Parenteau, N .
JOURNAL OF PROTEIN CHEMISTRY, 2001, 20 (04) :273-278
[2]   Desmoglein 4 is expressed in highly differentiated keratinocytes and trichocytes in human epidermis and hair follicle [J].
Bazzi, H ;
Getz, A ;
Mahoney, MG ;
Ishida-Yamamoto, A ;
Langbein, L ;
Wahl, JK ;
Christiano, AM .
DIFFERENTIATION, 2006, 74 (2-3) :129-140
[3]   Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system [J].
Bernett, MJ ;
Blaber, SI ;
Scarisbrick, IA ;
Dhanarajana, P ;
Thomspon, SM ;
Blaber, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (27) :24562-24570
[4]  
BIETH JG, 1995, METHOD ENZYMOL, V248, P59
[5]   INVIVO SIGNIFICANCE OF KINETIC CONSTANTS OF PROTEIN PROTEINASE-INHIBITORS [J].
BIETH, JG .
BIOCHEMICAL MEDICINE, 1984, 32 (03) :387-397
[6]   LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome [J].
Bitoun, E ;
Micheloni, A ;
Lamant, L ;
Bonnart, C ;
Tartaglia-Polcini, A ;
Cobbold, C ;
Al Saati, T ;
Mariotti, F ;
Mazereeuw-Hautier, J ;
Boralevi, F ;
Hohl, D ;
Harper, J ;
Bodemer, C ;
D'Alessio, M ;
Hovnanian, A .
HUMAN MOLECULAR GENETICS, 2003, 12 (19) :2417-2430
[7]  
Borgoño CA, 2004, MOL CANCER RES, V2, P257
[8]   Expression and functional characterization of the cancer-related serine protease, human tissue kallikrein 14 [J].
Borgono, Carla A. ;
Michael, Iacovos P. ;
Shaw, Julie L. V. ;
Luo, Liu-Ying ;
Ghosh, Manik C. ;
Soosaipillai, Antoninus ;
Grass, Linda ;
Katsaros, Dionyssios ;
Diamandis, Eleftherios P. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (04) :2405-2422
[9]   Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2 [J].
Bourgeois, L ;
BrillardBourdet, M ;
Deperthes, D ;
Juliano, MA ;
Juliano, L ;
Tremblay, RR ;
Dube, JY ;
Gauthier, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (47) :29590-29595
[10]   A proteolytic cascade of kallikreins in the stratum corneum [J].
Brattsand, M ;
Stefansson, K ;
Lundh, C ;
Haasum, Y ;
Egelrud, T .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 124 (01) :198-203