Search results for "amino acid transporter"

Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues.

2001

At least five distinct carrier proteins form the family of mammalian cationic amino acid transporters (CATs). We have cloned a cDNA containing the complete coding region of human CAT-3. hCAT-3 is glycosylated and localized to the plasma membrane. Transport studies in Xenopus laevis oocytes revealed that hCAT-3 is selective for cationic L-amino acids and exhibits a maximal transport activity similar to other CAT proteins. The apparent substrate affinity and sensitivity to trans-stimulation of hCAT-3 resembles most closely hCAT-2B. This is in contrast to rat and murine CAT-3 proteins that have been reported to display a very low activity and to be inhibited by neutral and anionic L-amino acid…

Putative role of cationic amino acid transporter‐3 in murine liver metabolism

2015

[68Ga]Ga-DO2A-(OBu-l-tyr)2: Synthesis, 68Ga-radiolabeling and in vitro studies of a novel 68Ga-DO2A-tyrosine conjugate as potential tumor tracer for …

2009

The synthesis, (68)Ga-labeling and in vitro study of the novel tyrosine chelate derivative [(68)Ga]Ga-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid-4,10-di-(O-butyl)-l-tyrosine ([(68)Ga]Ga-DO(2)A-(OBu-l-tyr)(2)) as a potential tracer for imaging tumor metabolism by positron emission tomography (PET) is presented. This approach combines the biological amino acid transporter targeting properties of l-tyrosine with the outstanding availability of (68)Ga(III) via the (68)Ge/(68)Ga generator. In vitro studies utilizing the F98-glioblastoma cell line revealed specific uptake of [(68)Ga]Ga-DO2A-(OBu-l-tyr)(2) that was comparable to that of the reference O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET)…

Activation of classical protein kinase C decreases transport via systems y+and y+L

2007

Activation of protein kinase C (PKC) downregulates the human cationic amino acid transporters hCAT-1 (SLC7A1) and hCAT-3 (SLC7A3) (Rotmann A, Strand D, Martiné U, Closs EI. J Biol Chem 279: 54185–54192, 2004; Rotmann A, Vekony N, Gassner D, Niegisch G, Strand D, Martine U, Closs EI. Biochem J 395: 117–123, 2006). However, others found that PKC increased arginine transport in various mammalian cell types, suggesting that the expression of different arginine transporters might be responsible for the opposite PKC effects. We thus investigated the consequence of PKC activation by phorbol-12-myristate-13-acetate (PMA) in various human cell lines expressing leucine-insensitive system y+[hCAT-1, h…

Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

2014

Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS), which metabolizes arginine to nitric oxide (NO) and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the…

CATs, a family of three distinct mammalian cationic amino acid transporters

1996

Three related mammalian carrier proteins that mediate the transport of cationic amino acids through the plasma membrane have been identified in murine and human cells (CAT for cationic amino acid transporter). Models of the CAT proteins in the membrane suggest they have 12 or 14 transmembrane domains connected by short hydrophilic loops and intracellular N- and C-termini. The transport activity of the CAT proteins is sensitive to trans-stimulation and independent of the presence of sodium ions. These features agree with the behaviour of carrier proteins mediating facilitated diffusion. The three CAT proteins, CAT-1, CAT-2A and CAT-2(B) are encoded by two different genes (CAT-1 and CAT-2). C…

Expression, regulation and function of carrier proteins for cationic amino acids.

2001

Different carrier proteins exhibiting distinct transport properties participate in cationic amino acid transport. There are sodium-independent systems, such as b+, y+, y+L and b0,+, and a sodium-dependent system B0,+, most of which have now been identified at the molecular level. In most non-epithelial cells, members of the cationic amino acid transporter (CAT) family mediating system y+ activity seem to be the major entry pathway for cationic amino acids. CAT proteins underlie complex regulation at the transcriptional, post-transcriptional and activity levels. Recent evidence indicates that individual CAT isoforms are necessary for providing the substrate for nitric oxide synthesis, for ex…

Identification of Cysteine Residues in Human Cationic Amino Acid Transporter hCAT-2A That Are Targets for Inhibition by N-Ethylmaleimide

2013

In most cells, cationic amino acids such as l-arginine, l-lysine, and l-ornithine are transported by cationic (CAT) and y(+)L (y(+)LAT) amino acid transporters. In human erythrocytes, the cysteine-modifying agent N-ethylmaleimide (NEM) has been shown to inhibit system y(+) (most likely CAT-1), but not system y(+)L (Devés, R., Angelo, S., and Chávez, P. (1993) J. Physiol. 468, 753-766). We thus wondered if sensitivity to NEM distinguishes generally all CAT and y(+)LAT isoforms. Transport assays in Xenopus laevis oocytes established that indeed all human CATs (including the low affinity hCAT-2A), but neither y(+)LAT isoform, are inhibited by NEM. hCAT-2A inhibition was not due to reduced tran…

Cationic Amino Acid Transporters (CATs)

2002

When the transport properties of mCAT-1 were described in 1991, the y+ carrier and major transporter for cationic amino acids seemed to be discovered. Today, we know that there are at least three different CAT isoforms that mediate y+ activity and the family might be growing. In addition, transport systems for cationic amino acids other than y + have been described and proteins that induce the respective transport activities have been identified. Consequently, the transport of cationic amino acids appears to be a complex process involving many proteins— carriers and possibly also regulatory proteins—whose expression is cell-specific and dependent on a variety of external stimuli. The multit…

The transport activity of the human cationic amino acid transporter hCAT-1 is downregulated by activation of protein kinase C

2001

1 The human cationic amino acid transporter hCAT-1 contains several consensus sequences for phosphorylation by protein kinase C (PKC). This study investigates the eAect of PKC activation on hCAT-1-mediated transport. 2 When expressed in Xenopus laevis oocytes, hCAT-1-mediated L-arginine transport was reduced to 44+3% after a 30 min treatment of the oocytes with 100 nM phorbol-12-myristate-13-acetate (PMA). 4a-phorbol-12,13-didecanoate (4a-PDD, 100 nM) had no eAect. 3 In EA.hy926 endothelial cells, maximal inhibition of hCAT-1-mediated L-arginine transport (to 3‐11% of control) was observed after treatment of the cells with 100 nM PMA for 4 h. A 20‐30 h exposure of the cells to 100 nM PMA le…