Tissue-specific promoter utilisation of the kallikrein-related peptidase genes, KLK5 and KLK7, and cellular localisation of the encoded proteins suggest roles in exocrine pancreatic function.
Abstract Tissue kallikrein (kallikrein 1) was first identified in pancreas and is the namesake of the kallikrein-related peptidase (KLK) family. KLK1 and the other 14 members of the human KLK family are encoded by 15 serine protease genes clustered at chromosome 19q13.4. Our Northern blot analysis of 19 normal human tissues for expression of KLK4 to KLK15 identified pancreas as a common expression site for the gene cluster spanning KLK5 to KLK13, as well as for KLK15 which is located adjacent to KLK1. Consistent with previous reports detailing the ability of KLK genes to generate organ- and disease-specific transcripts, detailed molecular and in silico analyses indicated that KLK5 and KLK7 generate transcripts in pancreas variant from those in skin or ovary. Consistently, we identified in the promoters of these KLK genes motifs which conform with consensus binding sites for transcription factors conferring pancreatic expression. In addition, immunohistochemical analysis revealed predominant localisation of KLK5 and KLK7 in acinar cells of the exocrine pancreas, suggesting roles for these enzymes in digestion. Our data also support expression patterns derived from gene duplication events in the human KLK cluster. These findings suggest that, in addition to KLK1, other related KLK enzymes will function in the exocrine pancreas.
Dong
Ying
Y
Hormone Dependent Cancer Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
Matigian
Nick
N
Harvey
Tracey J
TJ
Samaratunga
Hemamali
H
Hooper
John D
JD
Clements
Judith A
JA
D001665:Binding Sites; D015152:Blotting, Northern; D004063:Digestion; D006801:Humans; D007610:Kallikreins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005810:Multigene Family; D046790:Pancreas, Exocrine / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution; D014157:Transcription Factors
D012333:RNA, Messenger; D014157:Transcription Factors; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins