title: LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance.
abstract: Proteinase inhibitors are important negative regulators of proteinase action in vivo and are thus involved in several pathophysiological processes. Starting with the isolation of two new peptides from human blood filtrate, we succeeded in cloning a cDNA encoding the precursor protein for a novel 15-domain Kazal-type-related serine proteinase inhibitor. Two of the 15 domains almost exactly match the Kazal-type pattern, whereas the other 13 domains exhibit only four instead of six cysteine residues. Since the corresponding gene is expressed in several lympho-epithelial tissues, we termed this inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). For three of the 15 LEKTI domains, we demonstrated a significant trypsin-inhibiting activity. Recent results of another group show a relation between mutations within the LEKTI gene and the severe congenital disorder Netherton syndrome. In this review article, we give an overview of the already known data on the structure, processing, gene expression, and pathophysiological role of LEKTI.
authors.affiliation: IPF PharmaCeuticals GmbH, Feodor-Lynen-Strasse 31, 30625, Hannover, Germany. hj-maegert@gmx.de
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Mägert
authors.forename: Peter
authors.initials: P
authors.lastname: Kreutzmann
authors.forename: Ludger
authors.initials: L
authors.lastname: Ständker
authors.forename: Michael
authors.initials: M
authors.lastname: Walden
authors.forename: Katrin
authors.initials: K
authors.lastname: Drögemüller
authors.forename: Wolf Georg
authors.initials: WG
authors.lastname: Forssmann
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins; D017124:Conserved Sequence; D015870:Gene Expression; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000503:physiopathology; D008969:Molecular Sequence Data; D010455:Peptides / Q000097:blood; D017434:Protein Structure, Tertiary; D053491:Proteinase Inhibitory Proteins, Secretory; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors