The inhibition of Monocarboxylate Transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein.
Summary of "The inhibition of Monocarboxylate Transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein."
In mammalian cells MonoCarboxylate Transporters (MCTs) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4 and embigin for MCT2. In rat and rabbit erythrocytes MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT-PCR we have shown that Xenopus laevis oocytes contain endogenous basigin but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. By contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-lactate Km values for these constructs were determined and revealed that the transmembrane (TM) domains of an MCT, most probably TMs7-12, but not the C-terminus, are the major determinants of L-lactate affinity whilst the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin.
Affiliation
Journal Details
This article was published in the following journal.
Name: The Biochemical journal
ISSN: 1470-8728
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20695846
- DOI: http://dx.doi.org/10.1042/BJ20100890
Medical and Biotech [MESH] Definitions
Equilibrative Nucleoside Transporter 1
A subtype of equilibrative nucleoside transporter proteins that is sensitive to inhibition by 4-nitrobenzylthioinosine.
Equilibrative-nucleoside Transporter 2
A subtype of equilibrative nucleoside transporter proteins that is insensitive to inhibition by 4-nitrobenzylthioinosine.
Radiotherapy, Intensity-modulated
CONFORMAL RADIOTHERAPY that combines several intensity-modulated beams to provide improved dose homogeneity and highly conformal dose distributions.
Cationic Amino Acid Transporter 2
A high-affinity, low capacity system y+ amino acid transporter with strong similarity to CATIONIC AMINO ACID TRANSPORTER 1. The two isoforms of the protein, CAT-2A and CAT-2B, exist due to alternative mRNA splicing. The transporter has specificity for the transport of ARGININE; LYSINE; and ORNITHINE.
Excitatory Amino Acid Transporter 2
A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.
PubMed Articles
The ubiquitous enzyme carbonic anhydrase isoform II (CAII) has been shown to enhance transport activity of the proton-coupled monocarboxylate transporters MCT1 and MCT4 in a non-catalytic manner. In t...
Brain-derived neurotrophic factor (BDNF) promotes synaptic plasticity via an enhancement in expression of specific synaptic proteins. Recent results suggest that the neuronal monocarboxylate transport...
BACKGROUND: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate...
In the cyanobacterium Anabaena sp. strain PCC 7120, ORFs alr3026, alr3027 and all3028 encode a tripartite ATP-independent periplasmic transporter (TRAP-T). Wild-type filaments showed significant uptak...
The aim of this study was to determine the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, on monocarboxylate transporter 4 (M...
Clinical Trials
The P-glycoprotein (P-gp) is a membranous transporter that modulates the intracellular concentrations of many drugs and plays thus a major role in the efficacy of the therapeutics that act...
A Study of Therapeutic Amplitude-Modulated Electromagnetic Fields in Advanced Tumors
In vitro studies suggest that low levels of amplitude-modulated electromagnetic fields may modify cell growth. We have identified specific frequencies that may block cancer cell growth. We...
Intensity-Modulated Radiation Therapy in Treating Patients With Localized Prostate Cancer
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known...
Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
The study is being done to understand why some patients with epilepsy (disease of recurrence of seizures) do not respond very well to drug treatment with anticonvulsants. Despite the avai...
Genetic Epidemiology of Blood Lipids and Obesity - Ancillary to NGHS
To conduct a genetic epidemiologic study of the coronary heart disease (CHD) risk factors of blood lipids and obesity in Black and white girls who participated in the NHLBI-supported Natio...
