Cloning of mouse prostaglandin transporter PGT cDNA: species-specific substrate affinities

1  Departments of Medicine, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461; 2  Mammalian Genetics Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 We recently identifi...

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Published inAmerican journal of physiology. Regulatory, integrative and comparative physiology Vol. 277; no. 3; pp. 734 - R741
Main Authors Pucci, Michael L, Bao, Yi, Chan, Brenda, Itoh, Shigekazu, Lu, Run, Copeland, Neal G, Gilbert, Debra J, Jenkins, Nancy A, Schuster, Victor L
Format Journal Article
LanguageEnglish
Published United States 01.09.1999
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Abstract 1  Departments of Medicine, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461; 2  Mammalian Genetics Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A.   W. Wolkoff, and V. L. Schuster, Science 268: 866-869, 1995) and the human (hPGT) (Lu, R., and V. L. Schuster, J. Clin. Invest. 98: 1142-1149, 1996). Here we have cloned and expressed the mouse PGT (mPGT) cDNA. The tissue distribution of mPGT mRNA expression is significantly more restricted than that of rPGT and hPGT mRNA. Although the deduced amino acid sequence of mPGT is similar to the rat (91% identity) and human (82% identity) homologues, it has three regions of dissimilarity: amino acids 128-163 and 283-298, and valine 610 and isoleucine 611 (predicted to lie within putative transmembrane span 12). Affinities of hPGT, rPGT, and mPGT for several PG substrates differed, with hPGT having the highest [low Michaelis constant ( K m )] and mPGT the lowest affinity. A chimeric protein, linking the N-terminal domain of mPGT with the C-terminal domain of hPGT, had affinity for PGE 2 indistinguishable from that of hPGT, indicating that the C-terminal domain dictates K m . We mutagenized mouse valine 610 and isoleucine 611 to their corresponding human residues (methionine and glycine, respectively); however, these changes did not convert the inhibition constant of mPGT to that of hPGT. The mouse gene was localized to chromosome 9   in a region syntenic with the region of human chromosome 3 containing the hPGT gene. These studies highlight the species-dependence of tissue expression and function of PGT and lay the groundwork for the use of the mouse as a model system for the study of PGT function. carrier proteins; biological transport; molecular cloning; interspecific mouse backcross mapping
AbstractList We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A. W. Wolkoff, and V. L. Schuster, Science 268: 866–869, 1995) and the human (hPGT) (Lu, R., and V. L. Schuster, J. Clin. Invest. 98: 1142–1149, 1996). Here we have cloned and expressed the mouse PGT (mPGT) cDNA. The tissue distribution of mPGT mRNA expression is significantly more restricted than that of rPGT and hPGT mRNA. Although the deduced amino acid sequence of mPGT is similar to the rat (91% identity) and human (82% identity) homologues, it has three regions of dissimilarity: amino acids 128–163 and 283–298, and valine 610 and isoleucine 611 (predicted to lie within putative transmembrane span 12). Affinities of hPGT, rPGT, and mPGT for several PG substrates differed, with hPGT having the highest [low Michaelis constant ( K m )] and mPGT the lowest affinity. A chimeric protein, linking the N-terminal domain of mPGT with the C-terminal domain of hPGT, had affinity for PGE 2 indistinguishable from that of hPGT, indicating that the C-terminal domain dictates K m . We mutagenized mouse valine 610 and isoleucine 611 to their corresponding human residues (methionine and glycine, respectively); however, these changes did not convert the inhibition constant of mPGT to that of hPGT. The mouse gene was localized to chromosome 9 in a region syntenic with the region of human chromosome 3 containing the hPGT gene. These studies highlight the species-dependence of tissue expression and function of PGT and lay the groundwork for the use of the mouse as a model system for the study of PGT function.
1  Departments of Medicine, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461; 2  Mammalian Genetics Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A.   W. Wolkoff, and V. L. Schuster, Science 268: 866-869, 1995) and the human (hPGT) (Lu, R., and V. L. Schuster, J. Clin. Invest. 98: 1142-1149, 1996). Here we have cloned and expressed the mouse PGT (mPGT) cDNA. The tissue distribution of mPGT mRNA expression is significantly more restricted than that of rPGT and hPGT mRNA. Although the deduced amino acid sequence of mPGT is similar to the rat (91% identity) and human (82% identity) homologues, it has three regions of dissimilarity: amino acids 128-163 and 283-298, and valine 610 and isoleucine 611 (predicted to lie within putative transmembrane span 12). Affinities of hPGT, rPGT, and mPGT for several PG substrates differed, with hPGT having the highest [low Michaelis constant ( K m )] and mPGT the lowest affinity. A chimeric protein, linking the N-terminal domain of mPGT with the C-terminal domain of hPGT, had affinity for PGE 2 indistinguishable from that of hPGT, indicating that the C-terminal domain dictates K m . We mutagenized mouse valine 610 and isoleucine 611 to their corresponding human residues (methionine and glycine, respectively); however, these changes did not convert the inhibition constant of mPGT to that of hPGT. The mouse gene was localized to chromosome 9   in a region syntenic with the region of human chromosome 3 containing the hPGT gene. These studies highlight the species-dependence of tissue expression and function of PGT and lay the groundwork for the use of the mouse as a model system for the study of PGT function. carrier proteins; biological transport; molecular cloning; interspecific mouse backcross mapping
We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A. W. Wolkoff, and V. L. Schuster, Science 268: 866-869, 1995) and the human (hPGT) (Lu, R., and V. L. Schuster, J. Clin. Invest. 98: 1142-1149, 1996). Here we have cloned and expressed the mouse PGT (mPGT) cDNA. The tissue distribution of mPGT mRNA expression is significantly more restricted than that of rPGT and hPGT mRNA. Although the deduced amino acid sequence of mPGT is similar to the rat (91% identity) and human (82% identity) homologues, it has three regions of dissimilarity: amino acids 128-163 and 283-298, and valine 610 and isoleucine 611 (predicted to lie within putative transmembrane span 12). Affinities of hPGT, rPGT, and mPGT for several PG substrates differed, with hPGT having the highest [low Michaelis constant (K(m))] and mPGT the lowest affinity. A chimeric protein, linking the N-terminal domain of mPGT with the C-terminal domain of hPGT, had affinity for PGE2 indistinguishable from that of hPGT, indicating that the C-terminal domain dictates K(m). We mutagenized mouse valine 610 and isoleucine 611 to their corresponding human residues (methionine and glycine, respectively); however, these changes did not convert the inhibition constant of mPGT to that of hPGT. The mouse gene was localized to chromosome 9 in a region syntenic with the region of human chromosome 3 containing the hPGT gene. These studies highlight the species-dependence of tissue expression and function of PGT and lay the groundwork for the use of the mouse as a model system for the study of PGT function.
Author Lu, Run
Gilbert, Debra J
Pucci, Michael L
Jenkins, Nancy A
Bao, Yi
Copeland, Neal G
Itoh, Shigekazu
Schuster, Victor L
Chan, Brenda
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Snippet 1  Departments of Medicine, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461; 2  Mammalian Genetics Laboratory, ABL-Basic...
We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A. W. Wolkoff, and V. L. Schuster,...
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Enrichment Source
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StartPage 734
SubjectTerms Amino Acid Sequence
Animals
Antiporters - genetics
Antiporters - metabolism
Chromosome Mapping
Cloning, Molecular
DNA, Complementary - genetics
DNA, Complementary - isolation & purification
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Humans
Mice
Molecular Sequence Data
Organ Specificity
Organic Anion Transporters
Rats
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Sequence Alignment
Species Specificity
Title Cloning of mouse prostaglandin transporter PGT cDNA: species-specific substrate affinities
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