cationic amino acid transporter 2


Summary: 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.

Top Publications

  1. Martin L, Comalada M, Marti L, Closs E, MacLeod C, Martín Del Río R, et al. Granulocyte-macrophage colony-stimulating factor increases L-arginine transport through the induction of CAT2 in bone marrow-derived macrophages. Am J Physiol Cell Physiol. 2006;290:C1364-72 pubmed
    ..We conclude that BMM present mainly y(+)L activity and that, in response to GM-CSF, l-arginine transport augments through CAT2, thereby increasing the availability of this amino acid to the cell. ..
  2. Huang T, Tsai P, Huang C. HO-1 overexpression attenuates endotoxin effects on CAT-2 isozymes expression. J Surg Res. 2008;148:172-80 pubmed
    ..Induction of HO-1 overexpression also significantly attenuates the effects of endotoxin on the expression of iNOS and CAT-2 isozymes in septic rats. ..
  3. Jaeger K, Paulsen F, Wohlrab J. Characterization of cationic amino acid transporters (hCATs) 1 and 2 in human skin. Histochem Cell Biol. 2008;129:321-9 pubmed publisher
  4. Manner C, Nicholson B, MacLeod C. CAT2 arginine transporter deficiency significantly reduces iNOS-mediated NO production in astrocytes. J Neurochem. 2003;85:476-82 pubmed
    We have previously demonstrated that genetic ablation of cationic amino acid transporter 2 (Cat2) significantly inhibits nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in activated macrophages...
  5. Chaturvedi R, Asim M, Hoge S, Lewis N, Singh K, Barry D, et al. Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production. Gastroenterology. 2010;139:1686-98, 1698.e1-6 pubmed publisher
    ..Up-regulation of ODC in gastric macrophages impairs host defense against H pylori by suppressing iNOS-derived NO production. ..
  6. Rothenberg M, Doepker M, Lewkowich I, Chiaramonte M, Stringer K, Finkelman F, et al. Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung. Proc Natl Acad Sci U S A. 2006;103:14895-900 pubmed
    ..Thus, our data suggest that CAT2 regulates anti-inflammatory processes in the lungs via regulation of dendritic cell activation and subsequent T cell responses. ..
  7. Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, et al. Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol. 2006;36:1516-26 pubmed
  8. Nicholson B, Manner C, MacLeod C. Cat2 L-arginine transporter-deficient fibroblasts can sustain nitric oxide production. Nitric Oxide. 2002;7:236-43 pubmed
    ..The data demonstrate that fibroblasts and macrophages have differential dependence on CAT2-mediated L-arginine transport for NO synthesis. The important physiological implication of this finding is discussed. ..
  9. Singh K, Coburn L, Barry D, Asim M, Scull B, Allaman M, et al. Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response. Am J Physiol Gastrointest Liver Physiol. 2013;305:G225-40 pubmed publisher
    ..We assessed the role of cationic amino acid transporter 2 (CAT2), the inducible transporter of L-Arg, in DSS colitis...

More Information


  1. Yeramian A, Martin L, Serrat N, Arpa L, Soler C, Bertran J, et al. Arginine transport via cationic amino acid transporter 2 plays a critical regulatory role in classical or alternative activation of macrophages. J Immunol. 2006;176:5918-24 pubmed
    ..In conclusion, the increased arginine transport mediated by activators is strongly regulated by CAT2 expression, which could limit the function of macrophages. ..
  2. Suschek C, Mahotka C, Schnorr O, Kolb Bachofen V. UVB radiation-mediated expression of inducible nitric oxide synthase activity and the augmenting role of co-induced TNF-alpha in human skin endothelial cells. J Invest Dermatol. 2004;123:950-7 pubmed
    ..In summary, UVB induces iNOS mRNA and enzyme activity in HUDEC. Moreover, UVB augments CAT-2 expression through a TNF-alpha- dependent mechanism which essentially contributes to increased iNOS activity. ..
  3. Scalera F, Closs E, Flick E, Martens Lobenhoffer J, Boissel J, Lendeckel U, et al. Paradoxical effect of L-arginine: acceleration of endothelial cell senescence. Biochem Biophys Res Commun. 2009;386:650-5 pubmed publisher
    ..The most possible explanation for the paradoxical acceleration of senescence by L-arginine so far may be the translational and posttranslational activation of arginase II. ..
  4. Prasanth K, Prasanth S, Xuan Z, Hearn S, Freier S, Bennett C, et al. Regulating gene expression through RNA nuclear retention. Cell. 2005;123:249-63 pubmed
    ..CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage...
  5. Rotmann A, Closs E, Liewald J, Nawrath H. Intracellular accumulation of L-Arg, kinetics of transport, and potassium leak conductance in oocytes from Xenopus laevis expressing hCAT-1, hCAT-2A, and hCAT-2B. Biochim Biophys Acta. 2004;1660:138-43 pubmed
    ..Conductance measurements at symmetric concentrations of L-Arg (inside/outside) allowed us to determine KM and Vmax. The empty transporter of hCAT-2B featured an unexpected potassium conductance, which was inhibited by L-Arg. ..
  6. Abdelmagid S, Rickard J, McDonald W, Thomas L, Too C. CAT-1-mediated arginine uptake and regulation of nitric oxide synthases for the survival of human breast cancer cell lines. J Cell Biochem. 2011;112:1084-92 pubmed publisher
    ..In summary, several CAT isoforms are expressed in breast cancer cells. The CAT-1 isoform plays a role in arginine uptake and, together with PRL/E2-induced NOS, contribute to NO production for the survival of MCF-7 and T47D cells. ..
  7. Bernstein H, Stich C, Jäger K, Dobrowolny H, Wick M, Steiner J, et al. Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders. Neuropharmacology. 2012;62:237-46 pubmed publisher
    ..The reported increased expression of agmatinase suggests a functional relevance of the enzyme in the pathophysiology of human affective disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'. ..
  8. Singh K, Coburn L, Barry D, Boucher J, Chaturvedi R, Wilson K. L-arginine uptake by cationic amino acid transporter 2 is essential for colonic epithelial cell restitution. Am J Physiol Gastrointest Liver Physiol. 2012;302:G1061-73 pubmed publisher
    ..Uptake of L-Arg, and its metabolism by Arg1 to L-Orn and conversion to L-Pro by OAT is essential for colonic epithelial wound repair. ..
  9. Schwartz I, Chernichovsky T, Hagin D, Ingbir M, Reshef R, Chernin G, et al. Differential regulation of L-arginine transporters (cationic amino acid transporter-1 and -2) by peroxynitrite in rat mesangial cells. Nephrol Dial Transplant. 2006;21:3409-14 pubmed
    ..In contrast, CAT-1 mRNA expression and protein abundance were diminished. In rat mesangial cells, peroxynitrite augments arginine uptake via augmentation of CAT-2 while decreasing CAT-1 expression. ..
  10. Furesz T, Heath Monnig E, Kamath S, Smith C. Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. J Membr Biol. 2002;189:27-33 pubmed
    ..The identification and characterization of the various cationic amino-acid transporters of the human placenta have the potential to increase the understanding of the cellular mechanism of transplacental transfer. ..
  11. Talaue M, Venketaraman V, Hazbón M, Peteroy Kelly M, Seth A, Colangeli R, et al. Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis BCG infection. J Bacteriol. 2006;188:4830-40 pubmed
    ..The loss of Rv0522 gene-encoded arginine transport may have induced other cationic amino acid transport systems during intracellular growth of AS-1, allowing better survival within resting macrophages. ..
  12. Humphrey B, Kirsch S, Morris D. Molecular cloning and characterization of the chicken cationic amino acid transporter-2 gene. Comp Biochem Physiol B Biochem Mol Biol. 2008;150:301-11 pubmed publisher
    ..These results provide insight into the role of the cCAT-2 gene and its regulation of lysine and arginine utilization in aves. ..
  13. Thompson R, Pesce J, Ramalingam T, Wilson M, White S, Cheever A, et al. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathog. 2008;4:e1000023 pubmed publisher
    ..Thus, by controlling NOS2 and arginase activity, CAT2 functions as a potent regulator of immunity. ..
  14. Bass B, Hellwig S, Hundley H. A nuclear RNA is cut out for translation. Cell. 2005;123:181-3 pubmed
    ..It is then transported to the cytoplasm and translated into protein. These findings suggest that the nucleus may store RNAs destined for translation that then can be released, as needed, in response to specific cellular signals. ..
  15. Lin W, Tsai P, Huang C. Catecholamines' enhancement of inducible nitric oxide synthase-induced nitric oxide biosynthesis involves CAT-1 and CAT-2A. Anesth Analg. 2005;101:226-32, table of contents pubmed
    ..Furthermore, this catecholamine-enhanced L-arginine transport might involve CAT-1 and CAT-2A but not CAT-2 or CAT-2B. ..
  16. Wanasen N, MacLeod C, Ellies L, Soong L. L-arginine and cationic amino acid transporter 2B regulate growth and survival of Leishmania amazonensis amastigotes in macrophages. Infect Immun. 2007;75:2802-10 pubmed
    ..A possible role of mCAT-2B in supplying L-arginine directly to the parasites for their proliferation is discussed...
  17. Sala R, Rotoli B, Colla E, Visigalli R, Parolari A, Bussolati O, et al. Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+). Am J Physiol Cell Physiol. 2002;282:C134-43 pubmed
    ..It is concluded that modulation of endothelial arginine transport by TNF-alpha or lipopolysaccharide occurs exclusively through changes in CAT2B and CAT1 expression and is dissociated from stimulation of nitric oxide production. ..
  18. Visigalli R, Bussolati O, Sala R, Barilli A, Rotoli B, Parolari A, et al. The stimulation of arginine transport by TNFalpha in human endothelial cells depends on NF-kappaB activation. Biochim Biophys Acta. 2004;1664:45-52 pubmed
    ..These results indicate that in human endothelial cells the activation of NF-kappaB pathway mediates the TNFalpha effects on arginine transport. ..
  19. Nelin L, Krenz G, Chicoine L, Dawson C, Schapira R. L-Arginine uptake and metabolism following in vivo silica exposure in rat lungs. Am J Respir Cell Mol Biol. 2002;26:348-55 pubmed
    ..We conclude that the increase in NO production in silica-exposed lungs was associated with increased L-arg uptake from the vasculature, presumably resulting from increased CAT-1 and CAT-2, and by increased L-arg metabolism via arginase. ..
  20. Tsoporis J, Marks A, Van Eldik L, O Hanlon D, Parker T. Regulation of the S100B gene by alpha 1-adrenergic stimulation in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2003;284:H193-203 pubmed
    ..Our results suggest that alpha(1)-adrenergic stimulation induces the S100B gene after myocardial infarction through the PKC signaling pathway and that this induction is modulated by TEF-1 and RTEF-1. ..
  21. Schwartz I, Schwartz D, Traskonov M, Chernichovsky T, Wollman Y, Gnessin E, et al. L-Arginine transport is augmented through up-regulation of tubular CAT-2 mRNA in ischemic acute renal failure in rats. Kidney Int. 2002;62:1700-6 pubmed
    ..Ischemic ARF is associated with augmented tubular CAT-2 mRNA expression, which leads to enhanced l-Arg transport and increased NO production. This may contribute to the renal injury exhibited in iARF. ..
  22. Gao H, Wu G, Spencer T, Johnson G, Bazer F. Select nutrients in the ovine uterine lumen. III. Cationic amino acid transporters in the ovine uterus and peri-implantation conceptuses. Biol Reprod. 2009;80:602-9 pubmed publisher
    ..These results indicate that coordinate changes in SLC7A1, SLC7A2, and SLC7A3 expression in uterine endometria and conceptuses are likely important in transport of arginine that is critical to conceptus growth, development, and survival...
  23. Montañez R, Rodriguez Caso C, Sanchez Jimenez F, Medina M. In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells. Amino Acids. 2008;34:223-9 pubmed
    ..This analysis fulfills the flux control coefficient summation theorem and shows that both the low affinity transporter and arginase share the control of the fluxes through these metabolic pathways. ..
  24. Elsasser T, Kahl S, Macleod C, Nicholson B, Sartin J, Li C. Mechanisms underlying growth hormone effects in augmenting nitric oxide production and protein tyrosine nitration during endotoxin challenge. Endocrinology. 2004;145:3413-23 pubmed
  25. Nelin L, Nash H, Chicoine L. Cytokine treatment increases arginine metabolism and uptake in bovine pulmonary arterial endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2001;281:L1232-9 pubmed
    ..This suggests that induction of NOS and/or AR is linked to induction of CAT-2 in BPAECs and may represent a mechanism for maintaining L-Arg availability to NOS and/or AR...
  26. Habermeier A, Wolf S, Martine U, Graf P, Closs E. Two amino acid residues determine the low substrate affinity of human cationic amino acid transporter-2A. J Biol Chem. 2003;278:19492-9 pubmed
    ..In addition to the 42-amino acid domain, the adjacent transmembrane domain X seems to be involved in this function. ..
  27. Scumpia P, Sarcia P, Demarco V, Stevens B, Skimming J. Hypothermia attenuates iNOS, CAT-1, CAT-2, and nitric oxide expression in lungs of endotoxemic rats. Am J Physiol Lung Cell Mol Physiol. 2002;283:L1231-8 pubmed
    ..These findings suggest that hypothermia protects against intrapulmonary nitric oxide overproduction and nitric oxide-mediated lung injury by inhibiting transcription of iNOS, CAT-1, and CAT-2. ..
  28. Liu M, Tsai P, Yang C, Liu C, Chen C, Huang C. Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages. Acta Anaesthesiol Taiwan. 2006;44:73-81 pubmed
    ..In addition, timing of administration also affected this regulatory effect of propofol. ..
  29. Laspiur J, Burton J, Weber P, Kirkwood R, Trottier N. Short communication: amino acid transporters in porcine mammary gland during lactation. J Dairy Sci. 2004;87:3235-7 pubmed
    ..Porcine MT expresses CAT-1, CAT-2B, B(0,+), and ASCT1 during lactation. Preliminary findings indicate that B(0,+) mRNA abundance tended to decrease on d 17 compared with that on d 7. ..
  30. Wanasen N, Soong L. L-arginine metabolism and its impact on host immunity against Leishmania infection. Immunol Res. 2008;41:15-25 pubmed
    ..Various therapeutic approaches targeting L-arginine metabolic pathways during infections with Leishmania are also discussed. ..
  31. Huang C, Stevens B, Nielsen R, Slovin P, Fang X, Nelson D, et al. Interleukin-10 inhibition of nitric oxide biosynthesis involves suppression of CAT-2 transcription. Nitric Oxide. 2002;6:79-84 pubmed
    ..Moreover, our data suggests that transcriptional control of CAT-2 plays a role in IL-10 mediated influences upon nitric oxide biosynthesis. ..
  32. Casanello P, Sobrevia L. Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells. Circ Res. 2002;91:127-34 pubmed
    ..Alterations in L-arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies. ..
  33. Jager K, Wolf S, Dobrowolny H, Steiner J, Nave H, Maronde E, et al. Differential topochemistry of three cationic amino acid transporter proteins, hCAT1, hCAT2 and hCAT3, in the adult human brain. Amino Acids. 2013;44:423-33 pubmed publisher
    ..In contrast to what has been found in rodent brain, we detected hCAT2 and hCAT3 also in astrocytes. Overall, each hCAT has its characteristic, individual cerebral expression patterns, which, however, overlap with the others. ..
  34. Schwartz I, Ayalon R, Chernichovski T, Reshef R, Chernin G, Weinstein T, et al. Arginine uptake is attenuated through modulation of cationic amino-acid transporter-1, in uremic rats. Kidney Int. 2006;69:298-303 pubmed
    ..Renal and systemic arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These findings provide a possible novel mechanism to eNOS inactivation and endothelial dysfunction in uremia. ..
  35. Kirsch S, Humphrey B. Functional characterization of the chicken cationic amino acid transporter-2 isoforms. Comp Biochem Physiol B Biochem Mol Biol. 2010;156:279-86 pubmed publisher
    ..These data indicate that cCAT-2A is a low affinity, high velocity transporter for lysine and arginine and is the cCAT-2 isoform responsible for lysine and arginine transport in avian skeletal muscle. ..
  36. Chu L, Tsai P, Lee J, Yen C, Huang C. NF-kappaB inhibitors significantly attenuate the transcription of high affinity type-2 cationic amino acid transporter in LPS-stimulated rat kidney. Acta Anaesthesiol Taiwan. 2005;43:23-32 pubmed
    ..Furthermore, inhibition of NF-kappaB significantly attenuates NO biosynthesis through inhibition of iNOS, CAT-2, and CAT-2B, and, in turn, significantly reduces endotoxemia-induced renal injury. ..
  37. Yang C, Tsai P, Lee J, Huang C, Huang C. NF-kappaB inhibitors stabilize the mRNA of high-affinity type-2 cationic amino acid transporter in LPS-stimulated rat liver. Acta Anaesthesiol Scand. 2005;49:468-76 pubmed
    ..NF-kappaB inhibitors stabilize CAT-2 and CAT-2B mRNA in LPS-stimulated rat liver. The hepatic CAT-2/CAT-2B pathway may be a constitutive part of cytoprotective mechanisms against sepsis. ..
  38. McCord N, Ayuk P, McMahon M, Boyd R, Sargent I, Redman C. System y+ arginine transport and NO production in peripheral blood mononuclear cells in pregnancy and preeclampsia. Hypertension. 2006;47:109-15 pubmed
    ..This may create a relative deficiency of arginine in PBMCs favoring superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia. ..
  39. Yamasaki R, Zhang J, Koshiishi I, Sastradipura Suniarti D, Wu Z, Peters C, et al. Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Mol Cell Neurosci. 2007;35:573-84 pubmed
    ..The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO. ..
  40. Kagemann G, Sies H, Schnorr O. Limited availability of L-arginine increases DNA-binding activity of NF-kappaB and contributes to regulation of iNOS expression. J Mol Med (Berl). 2007;85:723-32 pubmed
  41. Jia Y, Pan C, Yang J, Liu X, Yuan W, Zhao J, et al. Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular adventitia of rats with sepsis. Clin Exp Pharmacol Physiol. 2006;33:1202-8 pubmed
    ..01). 6. The Arg/NOS/NO pathway was activated in the vascular adventitia of rats with sepsis shock. The L-Arg/NOS/NO pathway in the aortic adventitia may play an important role in the pathogenesis of sepsis and septic shock. ..
  42. Cao S, Gelwix C, Caldwell K, Caldwell G. Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J Neurosci. 2005;25:3801-12 pubmed
    ..Together, these data have mechanistic implications for movement disorders, because our results demonstrate that torsin proteins have the capacity to manage sources of cellular stress within DA neurons. ..
  43. Cui Z, Tuladhar R, Hart S, Marber M, Pearson J, Baydoun A. Rate of transport of l-arginine is independent of the expression of inducible nitric oxide synthase in HEK 293 cells. Nitric Oxide. 2005;12:21-30 pubmed
  44. Recker K, Klapperstück T, Kehlen A, Wohlrab J. The importance of cationic amino acid transporter expression in human skin. J Invest Dermatol. 2003;121:1552-3 pubmed
  45. Skimming J, Nasiroglu O, Huang C, Wood C, Stevens B, Haque I, et al. Dexamethasone suppresses iNOS yet induces GTPCH and CAT-2 mRNA expression in rat lungs. Am J Physiol Lung Cell Mol Physiol. 2003;285:L484-91 pubmed
    ..Our results support the idea that dexamethasone inhibits nitric oxide formation in a manner that is independent of tetrahydrobiopterin and arginine transport yet dependent on downregulation of iNOS mRNA expression. ..
  46. Schwartz D, Schwartz I, Gnessin E, Wollman Y, Chernichovsky T, Blum M, et al. Differential regulation of glomerular arginine transporters (CAT-1 and CAT-2) in lipopolysaccharide-treated rats. Am J Physiol Renal Physiol. 2003;284:F788-95 pubmed
    ..These results may correspond to the changes in glomerular iNOS and eNOS activity in sepsis. ..
  47. Li Volti G, Murabito P, Vanella L, Salafia S, Gullo A. Heme as a playmaker in the regulation of the nitric oxide system. Anesthesiology. 2007;107:355-6; author reply 356 pubmed
  48. Schwartz I, Iaina A, Benedict Y, Wollman Y, Chernichovski T, Brasowski E, et al. Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats. Kidney Int. 2004;65:1311-9 pubmed
    ..Increased nitric oxide formation may play a role in this process. ..
  49. Gonzalez M, Flores C, Pearson J, Casanello P, Sobrevia L. Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and -2 and membrane hyperpolarization in human umbilical vein endothelial cells. Pflugers Arch. 2004;448:383-94 pubmed
  50. Schnorr O, Suschek C, Kolb Bachofen V. The importance of cationic amino acid transporter expression in human skin. J Invest Dermatol. 2003;120:1016-22 pubmed
  51. Thakur S, Baydoun A. Post-transcriptional divergence in the regulation of CAT-2A, CAT-2B and iNOS expression by dexamethasone in vascular smooth muscle cells. Amino Acids. 2012;43:667-76 pubmed publisher
    ..Moreover, the effects of dexamethasone occur through a non-NF-?B-mediated action even though NF-?B is required for both processes. ..
  52. Kocher O, Pal R, Roberts M, Cirovic C, Gilchrist A. Targeted disruption of the PDZK1 gene by homologous recombination. Mol Cell Biol. 2003;23:1175-80 pubmed
  53. Leiva A, de Medina C, Salsoso R, Sáez T, San Martin S, Abarzua F, et al. Maternal hypercholesterolemia in pregnancy associates with umbilical vein endothelial dysfunction: role of endothelial nitric oxide synthase and arginase II. Arterioscler Thromb Vasc Biol. 2013;33:2444-53 pubmed publisher
    ..We speculate that elevated maternal circulating cholesterol is a factor leading to fetal endothelial dysfunction, which could have serious consequences to the growing fetus. ..