Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family

Michael P. Kavanaugh, Hao Wang, Zheng Zhang, Weibin Zhang, Yan Na Wu, Esther Dechant, R. Alan North, David Kabat

Research output: Contribution to journalArticle

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Abstract

A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C. L., Finley, K.,Kakuda, D. Kozad, C. A., and Wilkinson, M. F. (1990) Mol. Cell. Biol. 7, 3663-3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2α) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea cDNA from T lymphocytes (encoding CAT2β) with the exception of an apparent alternatively spliced sequence encoding a hydrophilic loop of 43 amino acids. The liver-specific sequence contains unique consensus sites for phosphorylation by cyclic AMP-dependent protein kinase and by protein kinase C. Injection of Xenopus oocytes with CAT2α or CAT2β messenger RNA resulted in expression of Na+-independent cationic amino acid transport that was detected by current measurements under voltage- clamp. Although the amino acid sequences of the isoforms differ in only 21 of 43 residues with the majority of substitutions being conservative, the apparent affinity of CAT2β for arginine uptake was 70-fold higher than the CAT2α isoform (K(m) 38 μM versus 2.7 mM). Neither isoform functioned as a receptor for ecotropic or amphotropic murine retroviruses. However, CAT1- CAT2 chimeric proteins that contain the first three putative extracellular loops of ecoR/CAT1 functioned as ecotropic receptors despite a diminished capacity to bind the viral envelope glycoprotein. The chimeric proteins also functioned as basic amino acid transporters with substrate affinities corresponding to the CAT2 isoform constituting the carboxyl-terminal portion. These results demonstrate that domains of these transporters can function in chimeric combinations to control viral receptor and transport functions.

Original languageEnglish (US)
Pages (from-to)15445-15450
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number22
StatePublished - Jun 3 1994

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Tea
Membrane Proteins
Liver
T-cells
Protein Isoforms
Amino Acids
Complementary DNA
Initiator Codon
Retroviridae
T-Lymphocytes
Basic Amino Acid Transport Systems
Proteins
Amino Acid Transport Systems
Basic Amino Acids
Phosphorylation
Terminator Codon
Clamping devices
Electric current measurement
Lymphocyte Activation
Xenopus

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kavanaugh, M. P., Wang, H., Zhang, Z., Zhang, W., Wu, Y. N., Dechant, E., ... Kabat, D. (1994). Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. Journal of Biological Chemistry, 269(22), 15445-15450.

Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. / Kavanaugh, Michael P.; Wang, Hao; Zhang, Zheng; Zhang, Weibin; Wu, Yan Na; Dechant, Esther; North, R. Alan; Kabat, David.

In: Journal of Biological Chemistry, Vol. 269, No. 22, 03.06.1994, p. 15445-15450.

Research output: Contribution to journalArticle

Kavanaugh, MP, Wang, H, Zhang, Z, Zhang, W, Wu, YN, Dechant, E, North, RA & Kabat, D 1994, 'Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family', Journal of Biological Chemistry, vol. 269, no. 22, pp. 15445-15450.
Kavanaugh MP, Wang H, Zhang Z, Zhang W, Wu YN, Dechant E et al. Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. Journal of Biological Chemistry. 1994 Jun 3;269(22):15445-15450.
Kavanaugh, Michael P. ; Wang, Hao ; Zhang, Zheng ; Zhang, Weibin ; Wu, Yan Na ; Dechant, Esther ; North, R. Alan ; Kabat, David. / Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 22. pp. 15445-15450.
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