The cDNA cloning and mRNA expression of rat protein C

Okafuji, Takaaki; Maekawa, Kazuyoshi; Nawa, Katsuhiko; Marumoto, Yasumasa

doi:10.1016/0167-4781(92)90035-x

Cited by 21 publications

(18 citation statements)

References 11 publications

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“…Although the liver is regarded as the major site of PC synthesis, 12,13,27,34 a few recent reports suggest that PC also may be synthesized extrahepatically. 13,14 For example, Northern blotting revealed PC mRNA in several rat tissues although at much lower levels than the liver, 14 and PC antigen was detected in human male reproductive tissues (eg, testis, epididymis, and prostate). 16 In this regard, human seminal plasma contains PC antigen at concentrations that are approximately 5% of those in plasma.…”

Section: Discussionmentioning

confidence: 99%

“…Although the liver appears to be the principal site of PC synthesis, 12 a few recent studies suggest that it also may be produced extrahepatically. 13,14 For example, several components of the PC anticoagulant system have been shown to be synthesized in the male reproductive tissues. In this regard, PC and protein S (a co-factor of APC 15 ) have been detected in Leydig cells of the human testis, 16,17 whereas PC inhibitor was detected throughout the male reproductive system 18 and in tubular cells of the human kidney.…”

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confidence: 99%

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Extrahepatic Expression and Regulation of Protein C in the Mouse

Yamamoto

Loskutoff

1998

The American Journal of Pathology

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Activated protein C (APC) acts as an anticoagulant by inhibiting coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C (PC) synthesis, the demonstration that other components of this system are produced extrahepatically raises the possibility that PC itself is synthesized in other tissues. We therefore used quantitative reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemistry to screen various murine tissues for PC expression. Relatively high levels of PC mRNA were detected in the kidney (35% of liver) and testis (22% of liver). PC mRNA and antigen were demonstrated in tubular epithelial cells in the renal cortex, in spermatogenic cells in the testis, and in epithelial cells in the epididymis. Low but significant levels of PC mRNA were detected in the epididymis (1.7% of the level in liver), brain (1.1% of liver), and lung (0.8% of liver). PC antigen was demonstrated in bronchial epithelial cells in the lung, in pyramidal neurons in the cerebrum, and in Purkinje cells in the cerebellum. The extrahepatic expression of PC mRNA (ie, in the kidney) was significantly decreased in mice with renal disease (eg, in MRL lpr/lpr mice with autoimmune lupus nephritis, in db/db mice with diabetic nephropathy, and in endotoxin-treated mice with acute renal injury). The decreased renal expression of PC may contribute to the increased procoagulant potential of the kidney during septic and inflammatory processes and to the progression of kidney disease associated with these conditions.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Extrahepatic Expression and Regulation of Protein C in the Mouse

Yamamoto

Loskutoff

1998

The American Journal of Pathology

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“…Next we made a 3Ј primer (3Јpr4) identical to the first 18 base pairs of the reported rat cDNA (Okafuji et al 1992). Comparison of these 18 base pairs with the human protein C cDNA shows a 78% identity in the first exon, making it likely that these 18 base pairs are located in the first exon of the rat protein C gene.…”

Section: Resultsmentioning

confidence: 99%

Identification of Evolutionarily Invariant Sequences in the Protein C Gene Promoter

Spek

Bertina

1998

J Mol Evol

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Recent studies on human protein C gene expression have revealed the presence of three transcription factor binding sites in close proximity to the transcription start site. Binding sites for the liver-enriched hepatocyte nuclear factors 1 and 3 (HNF-1 and HNF-3, respectively) are located immediately upstream of the transcription start site, whereas just downstream of the start site a presently unidentified transcription factor may bind. To identify other candidate transcription factor binding sites in the protein C promoter, we studied the promoter sequence identity in a number of evolutionarily close and more distant species: Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Homo sapiens, Cebus apella, Macaca mulatta, Callithrix jacchus, Papio hamadryas, Macaca fascicularis, and Rattus norvegicus. This analysis showed that a high degree of identity (78%) exists among the different primates. Comparison of the primate consensus sequence with the Rattus norvegicus protein C promoter sequence revealed the presence of seven identical regions (I to VII). Two of these regions overlap with established regulatory sequences for HNF-3 and HNF-1 (region VI) and for PCE-1 (region VII), respectively. The functional importance and the transcription factors that may bind to the other five identical regions are now to be determined.

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“…In addition to the human sequence, the sequences selected were as follows: factor IX; sheep, pig, rabbit, rat (Sarkar et al 1990), mouse (Wu et al 1990) and dog (Evans et al 1989): factor X; macaque, rat (Murakawa et al 1994a) and cow (Fung et al 1984): factor VII; macaque, dog (Murakawa et al 1994a) and rabbit (Brothers et al 1993): protein C;mouse (Murukawa et al 1994b;Tada et al 1992), rat (Okafuji et al 1992) and cow (Long et al 1984): prothrombin;cow (MacGillivray and Davie 1984), rat (Dihanich and Monard 1990) and mouse (Degen et al 1990). …”

Section: Alignment Of Amino Acid and Cdna Sequencesmentioning

confidence: 99%

Molecular reconstruction and homology modelling of the catalytic domain of the common ancestor of the haemostatic vitamin-K-dependent serine proteinases

1996

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The vitamin-K-dependent serine proteinases of coagulation have evolved by a process of gene duplication and divergence, acquiring along the way a considerable degree of functional diversity that has equipped them for their different roles in haemostasis. The cDNA sequences encoding the catalytic domains of the early mammalian ancestors of five vitamin-K-dependent factors (factors VII, IX and X, protein C and prothrombin) were reconstructed by employing cDNA sequence data from a range of extant mammals and by using established phylogenies. The cDNA sequence of the putative common ancestor of these early mammalian proteins was then reconstructed from the five sequences by using a deduced phylogeny that was different in a number of respects from those previously proposed. Factor IX is proposed to have branched off early on, followed by protein C and prothrombin and finally factors VII and X. Significant differences in mutation rates were observed between proteins within a species; factor IX exhibited a lower mutation rate than the other proteins, consistent with its early emergence. Differences in mutation rates were also observed between species for a given protein and these exhibited an inverse correlation with generation time. A biophysically plausible structure for the ancestral vitamin-K-dependent factor protein was constructed by comparative methods. Studies of the functional architecture of this model provide new insights into the evolution of protein-binding specificity in this family of proteins.

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The cDNA cloning and mRNA expression of rat protein C

Cited by 21 publications

References 11 publications

Extrahepatic Expression and Regulation of Protein C in the Mouse

Extrahepatic Expression and Regulation of Protein C in the Mouse

Identification of Evolutionarily Invariant Sequences in the Protein C Gene Promoter

Molecular reconstruction and homology modelling of the catalytic domain of the common ancestor of the haemostatic vitamin-K-dependent serine proteinases

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