SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor.
A previously unreported Kazal-type serine protease inhibitor, serine protease inhibitor Kazal type 9 (SPINK9), was identified in human skin. SPINK9 expression was strong in palmar epidermis, but not detectable or very low in non palmoplantar skin. Analysis of a human cDNA panel showed intermediate expression in thymus, pancreas, liver, and brain, and low or undetectable expression in other tissues. Using kallikrein-related peptidases (KLKs) 5, 7, 8, and 14, thrombin, trypsin, and chymotrypsin, inhibition with recombinant SPINK9 was seen only for KLK5 using low molecular weight substrates, with an apparent K(i) of 65 nM. Also KLK5 degradation of fibrinogen was totally inhibited by SPINK9. Slight inhibition of KLK8 using fibrinogen substrate could be observed using high concentrations of SPINK9. Analyses by surface plasmon resonance showed heterogeneous binding to SPINK9 of KLK5 and KLK8, but no binding of KLK7 or KLK14. KLK5 has been suggested to play a central role in skin desquamation as an initiating activating enzyme in proteolytic cascades formed by KLKs. An apparently KLK5-specific inhibitor, such as SPINK9, may play a significant regulatory role in such cascades. We suggest a possible role for SPINK9 in the site-specific epidermal differentiation of palms and soles.
Brattsand
Maria
M
Department of Dermatology and Venereology, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. maria.brattsand@dermven.umu.se
Stefansson
Kristina
K
Hubiche
Thomas
T
Nilsson
Stefan K
SK
Egelrud
Torbjörn
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
D005340:Fibrinogen; D007610:Kallikreins; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors; C542011:SPINK9 protein, human; C425336:KLK14 protein, human; C400147:KLK5 protein, human; C082472:KLK7 protein, human; C094799:KLK8 protein, human