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Activation of classical protein kinase C reduces the expression of human cationic amino acid transporter 3 (hCAT-3) in the plasma membrane.
Rotmann A
,
Vékony N
,
Gassner D
,
Niegisch G
,
Strand D
,
Martiné U
,
Closs EI
.
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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 PKCalpha-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.
Beckman,
Multiple G protein-coupled receptors initiate protein kinase C redistribution of GABA transporters in hippocampal neurons.
1999, Pubmed
Beckman,
Multiple G protein-coupled receptors initiate protein kinase C redistribution of GABA transporters in hippocampal neurons.
1999,
Pubmed
Closs,
Plasma membrane transporters for arginine.
2004,
Pubmed
Closs,
Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties.
1997,
Pubmed
,
Xenbase
Davis,
Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma.
1998,
Pubmed
Devés,
Transporters for cationic amino acids in animal cells: discovery, structure, and function.
1998,
Pubmed
,
Xenbase
González,
Regulation of the neuronal glutamate transporter excitatory amino acid carrier-1 (EAAC1) by different protein kinase C subtypes.
2002,
Pubmed
Gräf,
The transport activity of the human cationic amino acid transporter hCAT-1 is downregulated by activation of protein kinase C.
2001,
Pubmed
,
Xenbase
Hatzoglou,
Regulation of cationic amino acid transport: the story of the CAT-1 transporter.
2004,
Pubmed
Hosokawa,
Neuron-specific expression of cationic amino acid transporter 3 in the adult rat brain.
1999,
Pubmed
Hosokawa,
Cloning and characterization of a brain-specific cationic amino acid transporter.
1997,
Pubmed
Ito,
A new member of the cationic amino acid transporter family is preferentially expressed in adult mouse brain.
1997,
Pubmed
Johnson,
Progesterone acts through protein kinase C to remodel the cytoplasm as the amphibian oocyte becomes the fertilization-competent egg.
1997,
Pubmed
,
Xenbase
Koerner,
High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors.
1991,
Pubmed
Krotova,
Classical isoforms of PKC as regulators of CAT-1 transporter activity in pulmonary artery endothelial cells.
2003,
Pubmed
Martiny-Baron,
Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976.
1993,
Pubmed
Nishizuka,
The role of protein kinase C in cell surface signal transduction and tumour promotion.
,
Pubmed
Quick,
Second messengers, trafficking-related proteins, and amino acid residues that contribute to the functional regulation of the rat brain GABA transporter GAT1.
1997,
Pubmed
,
Xenbase
Racké,
Activation of L-arginine transport by protein kinase C in rabbit, rat and mouse alveolar macrophages.
1998,
Pubmed
Ramamoorthy,
Phosphorylation and regulation of antidepressant-sensitive serotonin transporters.
1998,
Pubmed
Robinson,
Signaling pathways take aim at neurotransmitter transporters.
2003,
Pubmed
Rotmann,
Protein kinase C activation promotes the internalization of the human cationic amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity.
2004,
Pubmed
,
Xenbase
Shih,
Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells.
1999,
Pubmed
Simons,
Purification of glutathione S-transferases by glutathione-affinity chromatography.
1981,
Pubmed
Smith,
Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
1988,
Pubmed
Torres,
Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.
2001,
Pubmed
Toullec,
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
1991,
Pubmed
Trotti,
Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters.
2001,
Pubmed
,
Xenbase
Vékony,
Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues.
2001,
Pubmed
,
Xenbase
Wolff,
Protein kinase C activation downregulates human organic anion transporter 1-mediated transport through carrier internalization.
2003,
Pubmed
,
Xenbase
Xiao,
Evidence for functional role of epsilonPKC isozyme in the regulation of cardiac Na(+) channels.
2001,
Pubmed
,
Xenbase