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http://purl.uniprot.org/citations/15680911http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15680911http://www.w3.org/2000/01/rdf-schema#comment"The secretory lympho-epithelial Kazal-type-inhibitor (LEKTI) is synthesized as a pro-LEKTI protein containing an N-terminal signal peptide and 15 potentially inhibitory domains. This inhibitor is of special interest because of its pathophysiological importance for the severe congenital disease Netherton syndrome. We showed that LEKTI is a potent inhibitor of a family of serine proteinases involved in extracellular matrix remodeling and its expression is downregulated in head and neck squamous cell carcinomas. To assess the role of C-terminal domains and N-terminal signal peptide in LEKTI secretion, we constructed deletion mutants of LEKTI, expressed them in HEK 293T cells, and analyzed their secretion behavior, stability, subcellular distribution, and proteinase inhibitory function. Pro-LEKTI is processed and secreted into the medium. On the basis of partial N-terminal sequencing and immunoblotting, the cleavage products are ordered from amino-to carboxy-terminal as follows: 37, 40, and 60kDa. Inhibitors of furin lead to enhanced secretion of unprocessed LEKTI, suggesting that processing was not required for secretion. Deletion of the N-terminal signal peptide of pro-LEKTI caused altered distribution of LEKTI from endoplasmic reticulum (ER) to cytoplasm and markedly reduced its stability, consistent with its failure to become secreted into the medium. Interestingly, when we deleted the C-terminal domains, stable partial LEKTI (LD-1-6) accumulated and still retained its association with ER but was not secreted. Recombinant LD-1-6 specifically inhibited the trypsin activity. We conclude that N-terminal signal peptide is required for LEKTI import into ER and elements present in C-terminal domains may have a role in regulating LEKTI secretion."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.org/dc/terms/identifier"doi:10.1016/j.abb.2004.12.012"xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Liu X."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Kang Y."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Wang M."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Jayakumar A."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Frederick M.J."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Clayman G.L."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"El-Naggar A.K."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Henderson Y."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Bebok Z."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Briggs K."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/author"Mitsudo K."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/name"Arch Biochem Biophys"xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/pages"89-102"xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/title"Consequences of C-terminal domains and N-terminal signal peptide deletions on LEKTI secretion, stability, and subcellular distribution."xsd:string
http://purl.uniprot.org/citations/15680911http://purl.uniprot.org/core/volume"435"xsd:string
http://purl.uniprot.org/citations/15680911http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15680911
http://purl.uniprot.org/citations/15680911http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15680911
http://purl.uniprot.org/uniprot/Q9NQ38#attribution-3579FCD4610C46044481FA91609FBBE6http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/15680911
http://purl.uniprot.org/uniprot/Q9NQ38#attribution-F7D3C0E54C8FF19C7AEDE101619D441Dhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/15680911
http://purl.uniprot.org/uniprot/#_B4DRW4-mappedCitation-15680911http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15680911
http://purl.uniprot.org/uniprot/#_B4DWS3-mappedCitation-15680911http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15680911