Evidence for ligand-independent homo-oligomerization of leptin receptor (OB-R) isoforms: A proposed mechanism permitting productive long-form signaling in the presence of excess short-form expression

Journal of Cellular Biochemistry

Volumn 73, Issue 2, 1999, Pages 278-288

  White, David W ^a   Tartaglia, Louis A ^a  

^a MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

Leptin; Obesity; Receptor oligomerization; Signal transduction

Indexed keywords

LEPTIN RECEPTOR;

ADIPOSE TISSUE; ANIMAL MODEL; ARTICLE; CELLULAR DISTRIBUTION; HORMONE RECEPTOR INTERACTION; IMMUNOPRECIPITATION; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; BIOPOLYMERS; CARRIER PROTEINS; CELL LINE; EPITOPES; HUMANS; JANUS KINASE 3; LEPTIN; LIGANDS; PROTEIN ISOFORMS; PROTEIN-TYROSINE KINASES; PROTEINS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 0033135272     PISSN: 07302312     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1097-4644(19990501)73:2<278::AID-JCB13>3.0.CO;2-W     Document Type: Article

References (36)

1. Barber DL, DeMartino JC, Showers MO, D'Andrea AD. 1994. A dominant negative erythropoietin (EPO) receptor inhibits EPO-dependent growth and blocks F-gp55-dependent transformation. Mol Cell Biol 14:2257-2265.
2. Baumann H, Morella KK, White DW, Dembski M, Bailon PS, Kim H, Lai C-F, Tartaglia LA. 1996. The full-length leptin receptor (OB-R) has signaling capabilities of IL-6-type cytokine receptors. Proc Natl Acad Sci USA 93:8374-8379.
3. Berti L, Kellerer M, Capp E, Haring HU. 1997. Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: Evidence for a PI3-kinase mediated effect. Diabetologia 40:606-609.
4. Bjorbaek C, Uotani S, da Silva B, Flier JS. 1998. Divergent signaling capabilities of the long and short isoforms of the leptin receptor. J Biol Chem 272:32686-32695.
5. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. 1995. Recombinant mouse ob protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546-549.
6. Chen H, Charlot O, Tartaglia LA, Woolf EA, Wen X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. 1996. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491-495.
7. Chen NG, Swick AG, Romsos DR. 1997. Leptin constrains acetylcholine-induced secretion from pancreatic islets of ob/ob mice. J Clin Invest 100:1174-1179.
8. Cohen J, Altaratz H, Zick Y, Klingmuller U, Neumann D. 1997. Phosphorylation of erythropoietin receptors in the endoplamsic reticulum by pervanadate-mediated inhibition of tyrosine phosphatases. Biochem J 327:391-397.
9. Darnell JE Jr. 1996. Reflections on Stat3, Stat5, and Stat6 as fat Stats. Proc Natl Acad Sci USA 93:6221-6224.
10. Devos R, Guisez Y, Van der Heyden J, White DW, Kalai M, Fountoulakis M, Plaetnick G. 1997. Ligand-independent dimerization of the extracellular domain of the leptin receptor and determination of the stoichiometry of leptin binding. J Biol Chem 272:18304-18310.
11. Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. 1997. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46:313-316.
12. Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC. 1996. Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci USA 93: 6231-6235.
13. Ghilardi N, Skoda RC. 1997. The leptin receptor activates Janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol 11:393-399.
14. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Freidman JM. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
15. Harlow E, Lane D. 1988. Antibodies: A laboratory manual, ed 1. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
16. Heldin C-H. 1995. Dimerization of cell surface receptors in signal transduction. Cell 80:213-223.
17. Hoggard N, Hunter L, Duncan JS, Williams LM, Trayhurn P, Mercer JG. 1997. Leptin and leptin receptor mRNA and protein expression in murine fetus and placenta. Proc Natl Acad Sci USA 94:11073-11078.
18. Ihle JN, Kerr IM. 1995. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet 11:69-74.
19. Kieffer TJ, Heller RS, Leech CA, Holz GG, Habener JF. 1997. Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 46:1087-1093.
20. Kishimoto T, Taga T, Akira S. 1994. Cytokine signal transduction. Cell 76:253-262.
21. Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JV, Bailey CJ, Bloom SR. 1997. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets, and in vivo, in mice. J Clin Invest 100:2729-2736.
22. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Freidman JM. 1996. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632-635.
23. Mercer JG, Hoggard N, Williams N, Lawrence CB, Hannah, LT Trayhurn P. 1996. Regulation of leptin receptor and NPY gene expression in the hypothalalmus of leptin-treated obese (ob/ob) and cold-exposed lean mice. FEBS Lett 387:113-116.
24. Nakashima K, Narazaki M, Taga T. 1997. Leptin receptor (OB-R) oligomerizes with itself but not with its closely related cytokine signal transducer. FEBS Lett 403: 79-82.
25. Pellymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
26. Perrot-Applanat M, Gualillo O, Pezet A, Vincent V, Edary M, Kelly PA. 1997. Dominant negative and cooperative effects of mutant forms of prolactin receptor. Mol Endocrinol 11:1020-1032.
27. Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dopbson PR, Postel-Vinay MC, Finidori J. 1997. A short isoform of the growth hormone receptor functions as a dominant negative inhibitor of the full-length receptor and generates large amounts of binding protein. Mol Endocrinol 11:265-273.
28. Shwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG. 1996. Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98:1101-1106.
29. Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin, WW, Cusin I, Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA. 1997. Direct effects of leptin on brown and white adipose tissue. J Clin Invest 100:2858-2864.
30. Stephens TW, Bashinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Hsiung HM, Kriauciunas A, Mackellar W, Rosteck PR, Schoner B, Smith D, Tinsley FC, Zhang XY, Helman M. 1995. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377:530-534.
31. Tanizawa Y, Okuya S, Ishihara H, Asano T, Yada T, Oka Y. 1997. Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells. Endocrinology 138:4513-4516.
32. Tartaglia LA, Dembski M, Wen X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Woolf EA, Monroe CA, Tepper RI. 1995. Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-1271.
33. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM. 1996. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nature Genet 14:95-97.
34. White DW, Kuropatwinski KK, Devos R, Baumann H, Tartaglia LA. 1997. Leptin receptor (OB-R) signaling: Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 272:4065-4071.
35. White DW, Wang Y, Chua SC Jr, Morgenstern JP, Leibel RL, Baumann H, Tartaglia LA. 1997. Constitutive and impaired signaling of leptin receptors containing the Gln-Pro extracellular domain fatty mutation. Proc Natl Acad Sci USA 94:10657-10662.
36. Zhang Y, Pronca R, Maffei M, Barone M, Leopold L, Freidman JM. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-431.