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- Ceder, Yvonne, et al.
(författare)
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Glandular kallikreins of the cotton-top tamarin: molecular cloning of the gene encoding the tissue kallikrein
- 2000
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Ingår i: DNA and Cell Biology. - : Mary Ann Liebert Inc. - 1044-5498 .- 1557-7430. ; 19:12, s. 721-727
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Tidskriftsartikel (refereegranskat)abstract
- The glandular kallikrein family is composed of structurally related serine proteases. Studies show that the mouse family encompasses at least 14 highly conserved functional genes, but of these only the tissue kallikarein has a human ortholog. In man, the tissue kallikrein display high sequence similarity with prostate specific antigen and human glandular kallikrein 2, suggesting that they evolved after the separation of primates and rodents. A phylogenetic study of the genes encoding glandular kallikreins in species evolutionarily located between rodents and man may reveal interesting details on how the gene family evolved, which in turn could yield information about the function of the proteins. Therefore, we have initiated a study of the glandular kallikreins of the cotton-top tamarin (Saguinus oedipus), a New World Monkey. Here, we report the cloning and nucleotide sequence of one of these, the tissue kallikrein gene. The gene of 4.4 kb is composed of five exons, and the structure is 90% similar to that of the orthologous human gene. It gives rise to a polypeptide of 261 amino acids, including a signal peptide of 17 residues, a pro-piece of 7 residues, and the mature protein of 237 residues with an estimated molecular mass of 26.3 kD. The similarity to the human prostate specific antigen and human glandular kallikrein 2 genes is 73% and 72%, respectively, including introns and flanking regions. The lower similarity to these genes compared with the human tissue kallikrein gene indicates that they, or a progenitor to them, arose in primates prior to the separation of New and Old World monkeys. Genomic Southern blots also show that the cotton-top tamarin genome encompasses at least one more glandular kallikrein gene.
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| 3. |
- Ceder, Yvonne
(författare)
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Structure, evolution and expression of glandular kallikrein genes
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate-specific antigen (PSA) is a worldwide used tool for the diagnosis and monitoring of prostate cancer. It is a serine protease and belongs to the family of glandular kallikreins. Humans have three classical glandular kallikreins, but it has been reported that rodents have many more. Lately, the family has been expanded to contain 12 new genes, KLK4–KLK15, that are situated at the same locus on 19q13.3–13.4 in humans. In our phylogenetic analysis, we were able to demonstrate that the classical glandular kallikrein genes can be considered a subgroup of the expanded glandular kallikrein family. The tissue kallikrein gene has 14 functional paralogs in the mouse and 10 in the rat, but there is only a single copy in artiodactyls, dogs and primates. The arginine esterase in the canine prostate is the only identified functional ortholog of the progenitor to human PSA and hK2. In contrast, KLK4–KLK15 are conserved in the mouse and rat, suggesting that they can be used as model systems to elucidate the physiological importance of these genes. We found that AREIII in the distal promoter region of KLK2 related genes contained deletions in all pseudogenes, whereas it is intact in all functional genes investigated in the present study, which implies that such deletions may represent a step in the process leading to the silencing of KLK2 genes. Repair of the AREIII in the cotton-top tamarin KLK2H2 pseudogene, led to restoration of full transcriptional activity, confirming the importance of this element. Both PSA and hK2 were found to be expressed in many non-prostatic tissues, but at much lower levels than in the prostate. Furthermore, it was shown that PSA in ileum exhibits comparable proteolytic activity and potential to form complexes with protease inhibitors as does PSA in prostate.
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| 7. |
- Lundwall, Åke, et al.
(författare)
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Molecular cloning of complementary DNA encoding mouse seminal vesicle-secreted protein SVSI and demonstration of homology with copper amine oxidases
- 2003
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Ingår i: Biology of Reproduction. - : Oxford University Press (OUP). - 1529-7268 .- 0006-3363. ; 69:6, s. 1923-1930
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Tidskriftsartikel (refereegranskat)abstract
- The primary structure of mouse SVS I was determined by peptide sequencing and nucleotide sequencing of cloned cDNA. The precursor molecule consists of 820 amino acid residues, including a signal peptide of 24 residues, and the mature polypeptide chain of 91 kDa has one site for potential N-linked glycosylation. The SVS I is homologous with amiloride-binding protein 1 (ABP1), a diamine oxidase. However, it probably lacks enzymatic activity, because the cDNA codes for His instead of Tyr at the position of the active-site topaquinon. The SVS I monomer probably binds one molecule of copper, because the His residues coordinated by Cu(II) are conserved. The SVS I gene consists of five exons and is situated on mouse chromosome 6,B2.3. It is located in a region of 100 kilobases (kb) containing several genes with homology to SVS 1, including the gene of ABP1 and two other proteins with homology to diamine oxidase. The locus is conserved on rat chromosome 4q24, but the homologous region on human chromosome 7q34-q36 solely contains ABP1. The other genes with homology to diamine oxidase were probably present in a progenitor of primates and rodents but were lost in the evolutionary lineage leading to humans-presumably during recombination between chromosomes. The estimated molecular mass of rat SVS I is 102 kDa (excluding glycosylation). The species difference in size of SVS I is caused by tandem repeats of 18 amino acid residues in the central part of the molecule: The mouse has seven repeats, and the rat has 12 repeats.
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| 8. |
- Lundwall, Åke, et al.
(författare)
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Semenogelin I and II, the predominant human seminal plasma proteins, are also expressed in non-genital tissues.
- 2002
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Ingår i: Molecular Human Reproduction. - 1460-2407. ; 8:9, s. 805-810
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Tidskriftsartikel (refereegranskat)abstract
- Semenogelin I (SgI) and semenogelin II (SgII) are the dominating protein components of the coagulum formed by freshly ejaculated human semen. The primary source of these proteins is the seminal vesicles and, apart from a small production of SgII in epididymis, they have not been detected in other tissues. In this report, we have re-examined the distribution of SgI and SgII transcripts and protein by RT-PCR and immunohistochemistry. Both SgI and SgII transcripts were demonstrated in several tissues, with the strongest signals coming from seminal vesicles, vas deferens, prostate, epididymis and trachea. Transcripts in the gastro-intestinal tract and skeletal muscle almost exclusively encoded SgI, whereas in kidney and testis, SgII transcripts were predominant. By immunohistochemistry, the basal cell layer of the secretory epithelium in prostate, trachea and bronchi was stained by antibodies recognizing both SgI and SgII. This is in contrast to the seminal vesicle and vas deferens, where the luminal cells were stained. The staining of skeletal muscle cells and a few scattered cells in the central nervous system suggests that semenogelin expression is not restricted to epithelial cells.
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| 9. |
- Lundwall, Åke, et al.
(författare)
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Semenogelin II gene is replaced by a truncated line 1 repeat in the cotton-top tamarin
- 2001
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Ingår i: Biology of Reproduction. - 1529-7268. ; 65:2, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- The human seminal vesicles secrete two proteins, semenogelin I and semenogelin II, at very high concentrations. It has previously been shown that the cotton-top tamarin (Sanguinus oedipus), a New World monkey, is lacking the semenogelin II gene. We have now determined the nucleotide sequence of DNA located 5--13 kilobases (kb) downstream of the tamarin semenogelin I gene---a region that in man is occupied by the semenogelin II gene. Two regions with homology to the human semenogelin II gene were identified in the tamarin DNA. The first region, of 3.5 kb, is homologous to DNA upstream of the human gene, and the second region, of 0.6 kb, is mainly derived from the second intron. Between these regions, equivalent to 594 base pairs (bp) upstream of the transcription initiation site to 12 bp downstream of the stop codon in the human semenogelin II gene, the cotton-top tamarin DNA carries a truncated LINE1 repeat. In another set of experiments, the tamarin DNA hybridizing to the mouse semenoclotin gene was investigated. It was concluded that hybridization is with the second intron of the semenoclotin gene, but very likely, the material does not represent a cotton-top tamarin semenoclotin gene. Thus, a mammalian ancestor probably carried a single gene that in the rodent lineage developed into the semenoclotin gene and in the primate lineage into a progenitor of the semenogelin genes.
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