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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 (Km)] 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 Km. 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
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  M. L. Pucci, S. Endo, T. Nomura, R. Lu, C. Khine, B. S. Chan, Y. Bao, and V. L. Schuster Coordinate control of prostaglandin E2 synthesis and uptake by hyperosmolarity in renal medullary interstitial cells Am J Physiol Renal Physiol, March 1, 2006; 290(3): F641 - F649. [Abstract] [Full Text] [PDF]
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B. S. Chan, S. Endo, N. Kanai, and V. L. Schuster Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT Am J Physiol Renal Physiol, June 1, 2002; 282(6): F1097 - F1102. [Abstract] [Full Text] [PDF]
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Y. Bao, M. L. Pucci, B. S. Chan, R. Lu, S. Ito, and V. L. Schuster Prostaglandin transporter PGT is expressed in cell types that synthesize and release prostanoids Am J Physiol Renal Physiol, June 1, 2002; 282(6): F1103 - F1110. [Abstract] [Full Text] [PDF]
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S. Endo, T. Nomura, B. S. Chan, R. Lu, M. L. Pucci, Y. Bao, and V. L. Schuster Expression of PGT in MDCK cell monolayers: polarized apical localization and induction of active PG transport Am J Physiol Renal Physiol, April 1, 2002; 282(4): F618 - F622. [Abstract] [Full Text] [PDF]
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 V. L. Schuster, S. Itoh, S. W. Andrews, R. M. Burk, J. Chen, K. M. Kedzie, D. W. Gil, and D. F. Woodward Synthetic Modification of Prostaglandin F2alpha Indicates Different Structural Determinants for Binding to the Prostaglandin F Receptor Versus the Prostaglandin Transporter Mol. Pharmacol., April 13, 2001; 58(6): 1511 - 1516. [Abstract] [Full Text]
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