Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1997-03-24
1999-10-05
Fitzgerald, David L.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
536 235, 4353201, 435 71, 530350, C12N 1512, C07K 14705
Patent
active
059622601
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a mammalian receptor for modified low-density lipoprotein (LDL), and in more detail relates to a mammalian vascular endothelial receptor for modified low-density lipoprotein.
BACKGROUND OF THE INVENTION
Vascular endothelial dysfunction has been pointed out as an important index in the early stages of progressive atherosclerosis. The vascular endothelial cell releases many sorts of humoral factors to keep circulatory homeostasis. The vascular endothelial function is inhibited by physical stimuli or various substances including the most important factor, oxidized low-density lipoprotein, which is a kind of modified low-density lipoproteins. For example, the vascular endothelial cell releases nitrogen monoxide as a vasohypotonic factor to adjust vascular tonus. The release of nitrogen monoxide is inhibited by the oxidized low-density lipoprotein.
It has been known that macrophages or vascular endothelial cells internalize the modified low-density lipoprotein through a receptor other than receptors for low-density lipoprotein. The macrophages internalize the modified low-density lipoprotein through scavenger receptors, which have already been structurally analyzed (cf., PCT Patent Japanese Publication Nos. 6(1994)-500765 and 6(1994)-508604, and Japanese Patent Provisional Publication No. 3(1991)-290184). The macrophages are then changed to foam cells, which are specific in arteriosclerotic focus. Since the macrophage scavenger receptors are not found in vascular endothelial cells, it has been anticipated that receptors of another structure are present in the vascular endothelial cells (cf., Hidenori Arai, Toru Kita, Oxidized LDL, Metabolism 28/4, 1991).
For the reasons mentioned above, it is necessary to analyze the structure of an endothelial receptor for modified low-density lipoprotein, namely the amino acid sequence of the receptor. However, the structure and the amino acid sequence have not yet been elucidated.
DISCLOSURE OF THE INVENTION
According to study of the present inventors, the structure of the vascular endothelial receptor for modified low-density lipoprotein is now elucidated. The amino acid sequences of the vascular endothelial receptor for modified low-density lipoprotein are set forth in SEQ ID NOS: 2, 4 and 6.
There is provided by the present invention a DNA sequence essentially encoding a mammalian vascular endothelial receptor for modified low-density lipoprotein.
The DNA sequence can be cDNA clones derived from the open reading frame of a gene corresponding to a native mammalian vascular endothelial receptor for modified low-density lipoprotein. The DNA sequence can also be a sequence which is capable of hybridization to the above-mentioned cDNA clones and encodes a biologically active mammalian vascular endothelial receptor for modified low-density lipoprotein. Further, the sequence can be degenerate as a result of the genetic code to the above-mentioned DNA sequences. The degenerate encodes the same biologically active receptor for modified low-density lipoprotein. Therefore, the present invention provides a DNA sequence set forth in SEQ ID NO: 1, 3 or 5(DNA having the sequence) or an analogue thereof, which corresponds to the region encoding a mammalian vascular endothelial receptor for modified low-density lipoprotein.
The present invention also provides a CDNA clone having a DNA sequence set forth in SEQ ID NO: 1, 3 or 5 or an analogue thereof, which corresponds to the region encoding a mammalian vascular endothelial receptor for modified low-density lipoprotein.
The present invention further provides a DNA sequence which is capable of hybridization to a cDNA clone of a DNA sequence set forth in SEQ ID NO: 1, 3 or 5 (DNA having the sequence) in 20% (v/v) formamide at 42.degree. C., and encodes a protein of a mammalian vascular endothelial cell, said protein having a function of binding a modified low-density lipoprotein (namely a receptor thereof).
The present invention furthermore provides a DNA sequence which is degene
REFERENCES:
patent: 5208144 (1993-05-01), Smith et al.
patent: 5380747 (1995-01-01), Medford et al.
patent: 5510466 (1996-04-01), Krieger et al.
patent: 5665872 (1997-09-01), Saito et al.
Ngo et al. (1994) In: The Protein Folding Problem and Tertiary Structure Prediction Merz et al (eds) Birkhauser, Boston, pp. 433, 492-495.
Ueda et al. (1993) Atherosclerosis 101:25-35 Abstract.
Itakura et al. (1990) LIPID 1:82-90-Abstract.
Mazzone et al (1982) Arteriosclerosis 2:487-497 Abstract.
Masaki Tomoo
Sawamura Tatsuya
Fitzgerald David L.
Nippon Chemiphar Co., Ltd.
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