4F2 cell-surface antigen heavy chain explained

4F2 cell-surface antigen heavy chain is a protein that in humans is encoded by the SLC3A2 (solute carrier family 3 member 2) gene.^{[1] [2]}

SLC3A2 comprises the heavy subunit of the large neutral amino acid transporter (LAT1) that is also known as CD98 (cluster of differentiation 98).^{[3] [4]}

Function

SLC3A2 is a member of the solute carrier family and encodes a cell surface, transmembrane protein with an alpha-amylase domain. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. It associates with integrins and mediates integrin-dependent signaling related to normal cell growth and tumorigenesis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

LAT1 is a heterodimeric membrane transport protein that preferentially transports neutral branched (valine, leucine, isoleucine) and aromatic (tryptophan, tyrosine, phenylalanine) amino acids.^[5] LAT is highly expressed in brain capillaries (which form the blood brain barrier) relative to other tissues.

A functional LAT1 transporter is composed of two proteins encoded by two distinct genes:

• 4F2hc/CD98 heavy subunit protein encoded by the SLC3A2 gene (this gene)^[6]
• CD98 light subunit protein encoded by the SLC7A5 gene^[7]

Interactions

SLC3A2 has been shown to interact with SLC7A7.^[8]

Additionally, SLC3A2 is a constituent member of the system xc- cystine/glutamate antiporter, complexing with SLC7A11.

See also

• Heterodimeric amino acid transporter

Further reading

• Rochelle JM, Watson ML, Oakey RJ, Seldin MF . A linkage map of mouse chromosome 19: definition of comparative mapping relationships with human chromosomes 10 and 11 including the MEN1 locus . Genomics . 14 . 1 . 26–31 . 1992 . 1358795 . 10.1016/S0888-7543(05)80278-2 .
• Michalak M, Quackenbush EJ, Letarte M . Inhibition of Na+/Ca2+ exchanger activity in cardiac and skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7 . J. Biol. Chem. . 261 . 1 . 92–5 . 1986 . 10.1016/S0021-9258(17)42436-7 . 2416754 . free .
• Gottesdiener KM, Karpinski BA, Lindsten T, Strominger JL, Jones NH, Thompson CB, Leiden JM . Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation . Mol. Cell. Biol. . 8 . 9 . 3809–19 . 1989 . 3265470 . 365439 . 10.1128/mcb.8.9.3809.
• Lindsten T, June CH, Thompson CB, Leiden JM . Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms . Mol. Cell. Biol. . 8 . 9 . 3820–6 . 1989 . 3265471 . 365440 . 10.1128/mcb.8.9.3820.
• Quackenbush E, Clabby M, Gottesdiener KM, Barbosa J, Jones NH, Strominger JL, Speck S, Leiden JM . Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth . Proc. Natl. Acad. Sci. U.S.A. . 84 . 18 . 6526–30 . 1987 . 3476959 . 299110 . 10.1073/pnas.84.18.6526 . 1987PNAS...84.6526Q . free .
• Lumadue JA, Glick AB, Ruddle FH . Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2 . Proc. Natl. Acad. Sci. U.S.A. . 84 . 24 . 9204–8 . 1988 . 3480538 . 299721 . 10.1073/pnas.84.24.9204 . free .
• Posillico JT, Srikanta S, Eisenbarth G, Quaranta V, Kajiji S, Brown EM . Binding of monoclonal antibody (4F2) to its cell surface antigen on dispersed adenomatous parathyroid cells raises cytosolic calcium and inhibits parathyroid hormone secretion . J. Clin. Endocrinol. Metab. . 64 . 1 . 43–50 . 1987 . 3782435 . 10.1210/jcem-64-1-43 .
• Hemler ME, Strominger JL . Characterization of antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines . J. Immunol. . 129 . 2 . 623–8 . 1982 . 10.4049/jimmunol.129.2.623 . 6177771 . 42283583 . free .
• Peters PG, Kamarck ME, Hemler ME, Strominger JL, Ruddle FH . Genetic and biochemical characterization of a human surface determinant on somatic cell hybrids: the 4F2 antigen . Somatic Cell Genet . 8 . 6 . 825–34 . 1983 . 6187076 . 10.1007/BF01543022 . 19788137 .
• Francke U, Foellmer BE, Haynes BF . Chromosome mapping of human cell surface molecules: monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11 . Somatic Cell Genet . 9 . 3 . 333–44 . 1983 . 6190235 . 10.1007/BF01539142 . 22972681 .
• Haynes BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer J, Mostowski HS, Thomas CA, Strominger JL, Fauci AS . Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes . J. Immunol. . 126 . 4 . 1409–14 . 1981 . 10.4049/jimmunol.126.4.1409 . 7204970 . 42367568 . free .
• Ohgimoto S, Tabata N, Suga S, Nishio M, Ohta H, Tsurudome M, Komada H, Kawano M, Watanabe N, Ito Y . Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules . J. Immunol. . 155 . 7 . 3585–92 . 1995 . 10.4049/jimmunol.155.7.3585 . 7561057 . 8787778 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Ohgimoto S, Tabata N, Suga S, Tsurudome M, Kawano M, Nishio M, Okamoto K, Komada H, Watanabe N, Ito Y . Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1 . J. Gen. Virol. . 77 . 11 . 2747–56 . 1996 . 8922468 . 10.1099/0022-1317-77-11-2747 .
• Courseaux A, Grosgeorge J, Gaudray P, Pannett AA, Forbes SA, Williamson C, Bassett D, Thakker RV, Teh BT, Farnebo F, Shepherd J, Skogseid B, Larsson C, Giraud S, Zhang CX, Salandre J, Calender A . Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1) . Genomics . 37 . 3 . 354–65 . 1997 . 8938448 . 10.1006/geno.1996.0570 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-Scale Concatenation cDNA Sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Tabata N, Ido M, Suga S, Ohgimoto S, Tsurudome M, Kawano M, Nishio M, Watanabe N, Okamoto K, Komada H, Sakurai M, Ito Y . Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced cell fusion mediated by HIV gp160 . Med. Microbiol. Immunol. . 186 . 2–3 . 115–23 . 1998 . 9403839 . 10.1007/s004300050053 . 7693336 .

Notes and References

1. Teixeira S, Di Grandi S, Kühn LC . Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus . J Biol Chem . 262 . 20 . 9574–80 . Aug 1987 . 10.1016/S0021-9258(18)47972-0 . 3036867 . free .
2. Web site: Entrez Gene: SLC3A2 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2.
3. Kucharzik T, Lugering A, Yan Y, Driss A, Charrier L, Sitaraman S, Merlin D . Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation . Lab. Invest. . 85 . 7 . 932–41 . 2005 . 15880135 . 10.1038/labinvest.3700289 . 19733993 .
4. Lemaître G, Gonnet F, Vaigot P, Gidrol X, Martin MT, Tortajada J, Waksman G . CD98, a novel marker of transient amplifying human keratinocytes . Proteomics . 5 . 14 . 3637–45 . 2005 . 16097038 . 10.1002/pmic.200401224 . 31954787 .
5. Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM . Selective expression of the large neutral amino acid transporter at the blood–brain barrier . Proc. Natl. Acad. Sci. U.S.A. . 96 . 21 . 12079–84 . 1999 . 10518579 . 18415 . 10.1073/pnas.96.21.12079 . 1999PNAS...9612079B . free .
6. Palacín M, Kanai Y . The ancillary proteins of HATs: SLC3 family of amino acid transporters . Pflügers Arch . 447 . 5 . 490–494 . 2004 . 14770309 . 10.1007/s00424-003-1062-7 . 25808108 .
7. Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y . CATs and HATs: the SLC7 family of amino acid transporters . Pflügers Arch . 447 . 5 . 532–542 . 2004 . 14770310 . 10.1007/s00424-003-1086-z . 11670040 .
8. Pfeiffer R, Rossier G, Spindler B, Meier C, Kühn L, Verrey F . Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family . EMBO J. . 18 . 1 . 49–57 . Jan 1999 . 9878049 . 1171101 . 10.1093/emboj/18.1.49 .