Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes

Zhong Guo, Károly Liliom, David J. Fischer, Ian C. Bathurst, L. David Tomei, Michael C. Kiefer, Gabor Tigyi

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphate, LPA) is a multifunctional lipid mediator found in a variety of organisms that span the phylogenetic tree from humans to plants. Although its physiological function is not clearly understood, LPA is a potent regulator of mammalian cell proliferation; it is one of the major mitogens found in blood serum. In Xenopus laevis oocytes, LPA elicits oscillatory Cl- currents. This current, like other effects of LPA, is consistent with a plasma membrane receptor-mediated activation of G protein-linked signal transduction pathways. Herein we report the identification of a complementary DNA from Xenopus that encodes a functional high-affinity LPA receptor. The predicted structure of this protein of 372 amino acids contains features common to members of the seven transmembrane receptor superfamily with a predicted extracellular amino and intracellular carboxyl terminus. An anti-sense oligonucleotide derived from the first 5-11 predicted amino acids, selectively inhibited the expression of the endogenous high-affinity LPA receptors in Xenopus oocytes, whereas the same oligonucleotide did not affect the low-affinity LPA receptor. Expression of the full-length cRNA in oocytes led to an increase in maximal Cl- current due to increased expression of the high-affinity LPA receptor, but activation of the low-affinity receptor was, again, unaffected. Oocytes expressing cRNA prepared from this clone showed no response to other lipid mediators including prostaglandins, leukotrienes, sphingosine 1-phosphate, sphingosylphosphorylcholine, and platelet-activating factor, suggesting that the receptor is highly selective for LPA.

Original languageEnglish (US)
Pages (from-to)14367-14372
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number25
DOIs
StatePublished - Dec 10 1996

Fingerprint

Lysophosphatidic Acid Receptors
Growth Factor Receptors
Molecular Cloning
Xenopus
Oocytes
Lipids
Complementary RNA
Amino Acids
Leukotrienes
Antisense Oligonucleotides
Xenopus laevis
Mitogens
GTP-Binding Proteins
Oligonucleotides
Prostaglandins
Signal Transduction
Complementary DNA
Clone Cells
Phosphates
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes. / Guo, Zhong; Liliom, Károly; Fischer, David J.; Bathurst, Ian C.; Tomei, L. David; Kiefer, Michael C.; Tigyi, Gabor.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 25, 10.12.1996, p. 14367-14372.

Research output: Contribution to journalArticle

Guo, Zhong ; Liliom, Károly ; Fischer, David J. ; Bathurst, Ian C. ; Tomei, L. David ; Kiefer, Michael C. ; Tigyi, Gabor. / Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 25. pp. 14367-14372.
@article{3dd56065c6dc4169b9cf6e08856936c9,
title = "Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes",
abstract = "Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphate, LPA) is a multifunctional lipid mediator found in a variety of organisms that span the phylogenetic tree from humans to plants. Although its physiological function is not clearly understood, LPA is a potent regulator of mammalian cell proliferation; it is one of the major mitogens found in blood serum. In Xenopus laevis oocytes, LPA elicits oscillatory Cl- currents. This current, like other effects of LPA, is consistent with a plasma membrane receptor-mediated activation of G protein-linked signal transduction pathways. Herein we report the identification of a complementary DNA from Xenopus that encodes a functional high-affinity LPA receptor. The predicted structure of this protein of 372 amino acids contains features common to members of the seven transmembrane receptor superfamily with a predicted extracellular amino and intracellular carboxyl terminus. An anti-sense oligonucleotide derived from the first 5-11 predicted amino acids, selectively inhibited the expression of the endogenous high-affinity LPA receptors in Xenopus oocytes, whereas the same oligonucleotide did not affect the low-affinity LPA receptor. Expression of the full-length cRNA in oocytes led to an increase in maximal Cl- current due to increased expression of the high-affinity LPA receptor, but activation of the low-affinity receptor was, again, unaffected. Oocytes expressing cRNA prepared from this clone showed no response to other lipid mediators including prostaglandins, leukotrienes, sphingosine 1-phosphate, sphingosylphosphorylcholine, and platelet-activating factor, suggesting that the receptor is highly selective for LPA.",
author = "Zhong Guo and K{\'a}roly Liliom and Fischer, {David J.} and Bathurst, {Ian C.} and Tomei, {L. David} and Kiefer, {Michael C.} and Gabor Tigyi",
year = "1996",
month = "12",
day = "10",
doi = "10.1073/pnas.93.25.14367",
language = "English (US)",
volume = "93",
pages = "14367--14372",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "25",

}

TY - JOUR

T1 - Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes

AU - Guo, Zhong

AU - Liliom, Károly

AU - Fischer, David J.

AU - Bathurst, Ian C.

AU - Tomei, L. David

AU - Kiefer, Michael C.

AU - Tigyi, Gabor

PY - 1996/12/10

Y1 - 1996/12/10

N2 - Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphate, LPA) is a multifunctional lipid mediator found in a variety of organisms that span the phylogenetic tree from humans to plants. Although its physiological function is not clearly understood, LPA is a potent regulator of mammalian cell proliferation; it is one of the major mitogens found in blood serum. In Xenopus laevis oocytes, LPA elicits oscillatory Cl- currents. This current, like other effects of LPA, is consistent with a plasma membrane receptor-mediated activation of G protein-linked signal transduction pathways. Herein we report the identification of a complementary DNA from Xenopus that encodes a functional high-affinity LPA receptor. The predicted structure of this protein of 372 amino acids contains features common to members of the seven transmembrane receptor superfamily with a predicted extracellular amino and intracellular carboxyl terminus. An anti-sense oligonucleotide derived from the first 5-11 predicted amino acids, selectively inhibited the expression of the endogenous high-affinity LPA receptors in Xenopus oocytes, whereas the same oligonucleotide did not affect the low-affinity LPA receptor. Expression of the full-length cRNA in oocytes led to an increase in maximal Cl- current due to increased expression of the high-affinity LPA receptor, but activation of the low-affinity receptor was, again, unaffected. Oocytes expressing cRNA prepared from this clone showed no response to other lipid mediators including prostaglandins, leukotrienes, sphingosine 1-phosphate, sphingosylphosphorylcholine, and platelet-activating factor, suggesting that the receptor is highly selective for LPA.

AB - Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphate, LPA) is a multifunctional lipid mediator found in a variety of organisms that span the phylogenetic tree from humans to plants. Although its physiological function is not clearly understood, LPA is a potent regulator of mammalian cell proliferation; it is one of the major mitogens found in blood serum. In Xenopus laevis oocytes, LPA elicits oscillatory Cl- currents. This current, like other effects of LPA, is consistent with a plasma membrane receptor-mediated activation of G protein-linked signal transduction pathways. Herein we report the identification of a complementary DNA from Xenopus that encodes a functional high-affinity LPA receptor. The predicted structure of this protein of 372 amino acids contains features common to members of the seven transmembrane receptor superfamily with a predicted extracellular amino and intracellular carboxyl terminus. An anti-sense oligonucleotide derived from the first 5-11 predicted amino acids, selectively inhibited the expression of the endogenous high-affinity LPA receptors in Xenopus oocytes, whereas the same oligonucleotide did not affect the low-affinity LPA receptor. Expression of the full-length cRNA in oocytes led to an increase in maximal Cl- current due to increased expression of the high-affinity LPA receptor, but activation of the low-affinity receptor was, again, unaffected. Oocytes expressing cRNA prepared from this clone showed no response to other lipid mediators including prostaglandins, leukotrienes, sphingosine 1-phosphate, sphingosylphosphorylcholine, and platelet-activating factor, suggesting that the receptor is highly selective for LPA.

UR - http://www.scopus.com/inward/record.url?scp=0029857994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029857994&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.25.14367

DO - 10.1073/pnas.93.25.14367

M3 - Article

VL - 93

SP - 14367

EP - 14372

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 25

ER -