We have previously shown that activation of PKC (protein kinase C) results in internalization of hCAT-1 [human CAT-1 (cationic amino acid transporter 1)] and a decrease in arginine transport [Rotmann, Strand, Martiné and Closs (2004) J. Biol. Chem. 279, 54185–54192]. However, others found increased transport rates for arginine in response to PKC activation, suggesting a differential effect of PKC on different CAT isoforms. Therefore we investigated the effect of PKC on hCAT-3, an isoform expressed in thymus, brain, ovary, uterus and mammary gland. In Xenopus laevis oocytes and human U373MG glioblastoma cells, hCAT-3-mediated L-arginine transport was significantly reduced upon treatment with compounds that activate classical PKC. In contrast, inactive phorbol esters and an activator of novel PKC isoforms had no effect. PKC inhibitors (including the PKCα-preferring Ro 31-8280) reduced the inhibitory effect of the PKC-activating compounds. Microscopic analyses revealed a PMA-induced reduction in the cell-surface expression of fusion proteins between hCAT-3 and enhanced green fluorescent protein expressed in X. laevis oocytes and glioblastoma cells. Western-blot analysis of biotinylated surface proteins demonstrated a PMA-induced decrease in hCAT-3 in the plasma membrane, but not in total protein lysates. Pretreatment with a PKC inhibitor also reduced this PMA effect. It is concluded that similar to hCAT-1, hCAT-3 activity is decreased by PKC via reduction of transporter molecules in the plasma membrane. Classical PKC isoforms seem to be responsible for this effect.
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Research Article|
March 15 2006
Activation of classical protein kinase C reduces the expression of human cationic amino acid transporter 3 (hCAT-3) in the plasma membrane
Alexander Rotmann;
Alexander Rotmann
1
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
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Nicole Vékony;
Nicole Vékony
1
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
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Davina Gassner;
Davina Gassner
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
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Günter Niegisch;
Günter Niegisch
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
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Dennis Strand;
Dennis Strand
†First Department of Internal Medicine, Johannes Gutenberg University, Obere Zahlbacher Strasse 63, 55101 Mainz, Germany
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Ursula Martiné;
Ursula Martiné
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
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Ellen I. Closs
Ellen I. Closs
2
*Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany
2To whom correspondence should be addressed (email Closs@mail.uni-mainz.de).
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Publisher: Portland Press Ltd
Received:
September 22 2005
Revision Received:
November 22 2005
Accepted:
December 07 2005
Accepted Manuscript online:
December 07 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 395 (1): 117–123.
Article history
Received:
September 22 2005
Revision Received:
November 22 2005
Accepted:
December 07 2005
Accepted Manuscript online:
December 07 2005
Citation
Alexander Rotmann, Nicole Vékony, Davina Gassner, Günter Niegisch, Dennis Strand, Ursula Martiné, Ellen I. Closs; Activation of classical protein kinase C reduces the expression of human cationic amino acid transporter 3 (hCAT-3) in the plasma membrane. Biochem J 1 April 2006; 395 (1): 117–123. doi: https://doi.org/10.1042/BJ20051558
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