Robert Lefkowitz

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Robert Lefkowitz Medalha Nobel
Nacionalidade Estados Unidos Estadunidense
Nascimento 15 de abril de 1943 (71 anos)
Local Nova Iorque
Alma mater Universidade Columbia
Prêmio(s) Prêmio Internacional da Fundação Gairdner (1988), Prêmio Shaw de Biologia e Medicina (2007), Medalha Nacional de Ciências (2007), Medalha do prêmio Nobel Nobel de Química (2012)

Robert J. Lefkowitz, M.D. (Nova Iorque, 15 de abril de 1943) é um médico estadunidense.

Foi laureado com o Nobel de Química de 2012, juntamente com Brian Kobilka, pelo estudo dos receptores acoplados à proteína G.[1]


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Publicações selecionadas[editar | editar código-fonte]

  • Mukherjee, C., Caron, M.G., Coverstone, M. and Lefkowitz, R.J.. (1975). "Identification of adenylate cyclase-coupled β-adrenergic receptors in frog erythrocytes with (-)[3H]alprenolol". J. Biol. Chem USA 250 (13): 4869–4876. PMID 238972.
  • Mukherjee, C., Caron, M.G. and Lefkowitz, R.J.. (1975). "Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites". Proc. Natl. Acad. Sci. USA 72 (5): 1945–1949. DOI:10.1073/pnas.72.5.1945. PMID 1057183.
  • Lefkowitz, R.J., Mullikin, D. and Caron, M.G.. (1976). "Regulation of beta-adrenergic receptors by 5'guanylylimidodiphosphate and other purine nucleotides". J. Biol. Chem USA 251 (15): 4688–4692. PMID 947904.
  • Williams, L.T. and Lefkowitz, R.J.. (1976). "α-adrenergic receptor identification by [3H]dihydroergocryptine binding". Science 192 (4241): 791–793. DOI:10.1126/science.4894. PMID 4894.
  • Limbird, L.E. and Lefkowitz, R.J.. (1977). "Resolution of beta-adrenergic receptor binding and adenylate cyclase activity by gel exclusion chromatography". J. Biol. Chem. 252 (2): 799–802. PMID 833154.
  • Caron, M.G., Srinivasan, Y., Pitha, J., Kochiolek, K. and Lefkowitz, R.J.. (1979). "Affinity chromatography of the β-adrenergic receptor". J. Biol. Chem. 254 (8): 2923–2927. PMID 218957.
  • Kent, R.S., De Lean, A. and Lefkowitz, R.J.. (1980). "Quantitative analysis of beta-adrenergic receptor interactions: Resolution of high and low affinity states of the receptor by computer modeling of ligand binding data". Mol. Pharmacol. USA 17 (1): 14–23. PMID 6104284.
  • Limbird, L.E., Gill, M. and Lefkowitz, R.J.. (1980). "Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system". Proc. Natl. Acad. Sci. USA 77 (2): 775–779. DOI:10.1073/pnas.77.2.775. PMID 6244585.
  • De Lean, A., Stadel, J.M. and Lefkowitz, R.J. (1980). "A ternary complex model explains the agonist-specific binding properties of the adenylate-cyclase coupled beta-adrenergic receptor". J. Biol. Chem. 255 (15): 7108–7117. PMID 6248546.
  • Lavin, T., Heald, S., Jeffs, P., Shorr, R., Lefkowtiz, R.J. and Caron, M.G.. (1981). "Photoaffinity labeling of the β-adrenergic receptor". J. Biol. Chem. 256 (22): 11944–11950. PMID 6271767.
  • DeLean, A., Hancock, A. and Lefkowitz, R.J.. (1982). "Validation and statistical analysis of a computer modeling method for quantitative analysis of radiolgiand binding data for mixtures of pharmacological receptor subtypes". Mol. Pharmacol. USA 21 (1): 5–16. PMID 6982395.
  • Stadel, J.M., Nambi, P., Lavin, T.N., Heald, S.L., Caron, M.G. and Lefkowitz, R.J.. (1982). "Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase: Structural alterations in the beta-adrenergic receptor revealed by photoaffinity labelling". J. Biol. Chem. 257 (16): 9242–9245. PMID 6125504.
  • Cerione, R.A., Strulovici, B., Benovic, J.L., Lefkowitz, R.J. and Caron, M.G.. (1983). "Pure beta-adrenergic receptor: the single polypeptide confers catecholamine responsiveness to adenylate cyclase". Nature 306 (5943): 562–566. DOI:10.1038/306562a0. PMID 6316161.
  • Stadel, J.M., Nambi, P., Shorr, R.G.L., Sawyer, D.F., Caron, M.G. and Lefkowitz, R.J.. (1983). "Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta adrenergic receptor". Proc. Natl. Acad. Sci. USA 80 (11): 3173–3177. DOI:10.1073/pnas.80.11.3173. PMID 6304694.
  • Strulovici, B., Cerione, R.A., Kilpatrick, B.F., Caron, M.G. and Lefkowitz, R.J.. (1984). "Direct demonstration of impaired functionality of a purified desensitized β-adrenergic receptor in a reconstituted system". Science 225 (4664): 837–840. DOI:10.1126/science.6089331. PMID 6089331.
  • Cerione, R.A., Sibley, D.R., Codina, J., Benovic, J.L., Winslow, J., Neer, E.J., Birnbaumer, L., Caron, M.G. and Lefkowitz, R.J.. (1984). "Reconstitution of a hormone-sensitive adenylate cyclase system: The pure β-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit". J. Biol. Chem. 259 (16): 9979–9982. PMID 6088509.
  • Benovic, J.L., Shorr, R.G.L., Caron, M.G. and Lefkowitz, R.J.. (1984). "The mammalian β2-adrenergic receptor: Purification and characterization". Biochemistry USA 23 (20): 4510–4518. DOI:10.1021/bi00315a002. PMID 6093858.
  • Sibley, D.R., Strasser, R.H., Caron, M.G. and Lefkowitz, R.J.. (1985). "Homologous desensitization of adenylate cyclase is associated with phosphorylation of the β-adrenergic receptor". J. Biol. Chem USA 260 (7): 3883–3886. PMID 2858484.
  • Regan, J.W., Nakata, H., DeMarinis, R.M., Caron, M.G. and Lefkowitz, R.J.. (1985). "Purification and characterization of the human platelet alpha 2-adrenergic receptor". J. Biol. Chem USA 261 (8): 3894–3900. PMID 3005306.
  • Lomasney, J.W., Leeb-Lundberg, L.M.F., Cotecchia, S., Regan, J.W., DeBernardis, J.F., Caron, M.G. and Lefkowitz, R.J.. (1986). "Mammalian alpha 1-adrenergic receptor. Purification and characterization of the native receptor ligand binding subunit". J. Biol. Chem USA 261 (17): 7710–7716. PMID 3011796.
  • Dixon, R.A.F., Kobilka, B.K., Strader, D.J., Benovic, J.L., Dohlman, H.G., Frielle, T., Bolanowski, M.A., Bennett, C.D., Rands, E., Diehl, R.E., Mumford, R.A., Slater, E.E., Sigal, I.S., Caron, M.G., Lefkowitz, R.J. and Strader, C.D.. (1986). "Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin". Nature 321 (6065): 75–79. DOI:10.1038/321075a0. PMID 3010132.
  • Benovic, J.L., Strasser, R.H., Caron, M.G. and Lefkowitz, R.J.. (1986). "β-Adrenergic receptor kinase: Identification of a novel protein kinase which phosphorylates the agonist-occupied form of the receptor". Proc. Natl. Acad. Sci. USA 83 (9): 2797–2810. DOI:10.1073/pnas.83.9.2797. PMID 2871555.
  • Benovic, J.L., Mayor, F., Jr., Somers, R.L., Caron, M.G. and Lefkowitz, R.J.. (1986). "Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase". Nature 321 (6073): 869–872. DOI:10.1038/321869a0. PMID 3014340.
  • Kobilka, B.K., Matsui, H., Kobilka, T.S., Yang-Feng, T.L., Francke, U., Caron, M.G., Lefkowitz, R.J. and J.W. Regan. (1987). "Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor". Science 238 (4827): 650–656. DOI:10.1126/science.2823383. PMID 2823383.
  • Frielle, T., Collins, S., Daniel, K.W., Caron, M.G., Lefkowitz, R.J. and Kobilka, B.K.. (1987). "Cloning of the cDNA for the human β1 adrenergic receptor". Proc. Natl. Acad. Sci. USA 84 (22): 7920–7924. DOI:10.1073/pnas.84.22.7920. PMID 2825170.
  • Benovic, J.L., Kuhn, H., Weyand, I., Codina, J., Caron, M.G. and Lefkowitz, R.J.. (1987). "Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein)". Proc. Natl. Acad. Sci. USA 84 (24): 8879–8882. DOI:10.1073/pnas.84.24.8879. PMID 2827157.
  • Cotecchia, S., Schwinn, D.A., Randall, R.R., Lefkowitz, R.J., Caron, M.G. and Kobilka, B.K. (1988). "Molecular cloning and expression of the cDNA for the hamster alpha1-adrenergic receptor". Proc. Natl. Acad. Sci. USA 85 (19): 7159–7163. DOI:10.1073/pnas.85.19.7159. PMID 2845398.
  • Kobilka, B.K., Kobilka, T.S., Daniel, K., Regan, J.W., Caron, M.G. and Lefkowitz, R.J.. (1988). "Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity". Science 240 (4857): 1310–1316. DOI:10.1126/science.2836950. PMID 2836950.
  • O'Dowd, B.F., Hnatowich, M., Regan, J.W., Leader, W.M., Caron, M.G. and Lefkowitz, R.J.. (1988). "Site-directed mutagenesis of the cytoplasmic domains of the human β2-adrenergic receptor: Localization of regions involved in G protein-receptor coupling". J. Biol. Chem. 263 (31): 15985–15992. PMID 2846532.
  • Fargin, A., Raymond, R.J., Lohse, M.J., Kobilka, B.K., Caron, M.G. and Lefkowitz, R.J.. (1988). "The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor". Nature 335 (6188): 358–360. DOI:10.1038/335358a0. PMID 3138543.
  • Regan, J.W., Kobilka, T.S., Yang-Feng, T.L., Caron, M.G. and Lefkowitz, R.J. (1988). "Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype". Proc. Natl. Acad. Sci. USA 85 (17): 6301–6305. DOI:10.1073/pnas.85.17.6301. PMID 2842764.
  • Hausdorff, W.P., Bouvier, M., O'Dowd, B.F., Irons, G.P., Caron, M.G. and Lefkowitz, R.J.. (1989). "Phosphorylation sites on two domains of the β2-adrenergic receptor are involved in distinct pathways of receptor desensitization". J. Biol. Chem. 264 (21): 12657–12665. PMID 2545714.
  • Benovic, J.L., DeBlasi, A., Stone, W.C., Caron, M.G. and Lefkowitz, R.J.. (1989). "β-Adrenergic receptor kinase: Primary structure delineates a multigene family". Science 246 (4927): 235–240. DOI:10.1126/science.2552582. PMID 2552582.
  • Schwinn, D.A., Lomasney, J.W., Lorenz, W., Szklut, Fremeau, R.T., Jr., Yang-Feng, T.L., Caron, M.G., Lefkowitz, R.J. and Cotecchia, S.. (1990). "Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype". J. Biol. Chem. 265 (14): 8183–8187. PMID 1970822.
  • Lomasney, J.W., Lorenz, W., Allen, L.F., King, K., Regan, J.W., Yang-Feng, T.L., Caron, M.G. and Lefkowitz, R.J.. (1990). "Expansion of the Alpha2-adrenergic receptor family: Cloning and Characterization of a human Alpha2-adrenergic receptor subtype, the gene for which is located on chromosome 2". Proc. Natl. Acad. Sci. USA 87 (13): 5094–5098. DOI:10.1073/pnas.87.13.5094. PMID 2164221.
  • Lohse, M.J., Benovic, J.L., Codina, J., Caron, M.G. and Lefkowitz, R.J.. (1990). "beta-Arrestin: a protein that regulates beta-adrenergic receptor function". Science 248 (4962): 1547–1550. DOI:10.1126/science.2163110. PMID 2163110.
  • Cotecchia, S., Exum, S., Caron, M.G. and Lefkowitz, R.J.. (1990). "Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function". Proc. Natl. Acad. Sci. USA 87 (8): 2896–2900. DOI:10.1073/pnas.87.8.2896. PMID 2158097.
  • Lorenz, W., Inglese, J., Palczewski, K., Onorato, J.J., Caron, M.G. and Lefkowitz, R.J.. (1991). "The receptor kinase family: Primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase". Proc. Natl. Acad. Sci. USA. 88 (19): 8715–8719. DOI:10.1073/pnas.88.19.8715. PMID 1656454.
  • Lomasney, J.W., Cotecchia, S., Lorenz, W., Leung, W-Y., Schwinn, D.A., Yang-Feng, T.L., Brownstein, Lefkowitz, R.J., and Caron, M.G.. (1991). "Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5". J. Biol. Chem. 266 (10): 6365–6369. PMID 1706716.
  • Attramadal, H., Arriza, J.L., Aoki, C., Dawson, T.M., Codina, J., Kwatra, M.M., Snyder, S.H., Caron, M.G. and Lefkowitz, R.J.. (1992). "Beta-arrestin2, a novel member of the arrestin/Beta-arrestin gene family". J. Biol. Chem. 267 (25): 17882–17890. PMID 1517224.
  • Kjelsberg, M.A., Cotecchia, S., Ostrowski, J., Caron, M.G. and Lefkowitz, R.J.. (1992). "Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation". J. Biol. Chem. 267 (3): 1430–1433. PMID 1346134.
  • Samama, P., Cotecchia, S., Costa, T. and Lefkowitz, R.J.. (1993). "A mutation-induced activated state of the beta 2-adrenergic receptor-extending the ternary complex model". J. Biol. Chem. 268 (7): 4625–4636. PMID 8095262.
  • Lefkowitz, R.J.. (1993). "G protein-coupled receptor kinases". Cell. USA 74 (3): 409–412. PMID 8394218.
  • Bond, R.A., Leff, P., Johnson, T.D., Milano, C.A., Rockman, H.A., McMinn, T.F., Apparsundaram, S., Hyek, M.F., Kenakin, T.P., Allen, L.F. and Lefkowitz, R.J.. (1995). "Physiologic effects of inverse agonists in transgenic mice with myocardial overexpression of the beta 2-adrenoceptor". Nature. USA 374 (6519): 272–276. DOI:10.1038/374272a0. PMID 7885448.
  • Lin, F-T., Daaka, Y. and Lefkowitz, R.J.. (1998). "β-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor". J. Biol. Chem. 273 (48): 31640–31643. PMID 9822622.
  • Luttrell, L.M., Ferguson, S.S.G., Daaka, Y., Miller, W.E., Maudsley, S., Della Rocca, G.J., Lin, F-T., Kawakatsu, H., Owada, K., Luttrell, D.K., Caron, M.G. and Lefkowitz, R.J.. (1999). "Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes". Science. USA 283 (5402): 655–661. DOI:10.1126/science.283.5402.655. PMID 9924018.
  • Bohn, L.M., Lefkowitz, R.J. Gainetdinov, R.R., Peppel, K., Caron, M.D. and Lin, F-T.. (1999). "Enhanced morphine analgesia in mice lacking βarrestin-2". Science. USA 286 (5449): 2495–2498. DOI:10.1126/science.286.5449.2495. PMID 10617462.
  • Lefkowitz, R.J.. (2000). "The superfamily of heptahelical receptors". Nature Cell Biology. USA 2 (7): E132–E136. DOI:10.1038/35017152. PMID 10878827.
  • Shenoy, S.K., McDonald, P.H., Kohout, T.A., Lefkowitz, R.J.. (2001). "Regulation of Receptor Fate by Ubiquitination of Activated β2-Adrenergic Receptor and β-Arrestin". Science. USA 294 (5545): 1307–1313. DOI:10.1126/science.1063866. PMID 11588219.
  • Luttrell, L.M., Roudabush, F.L., Choy, E.W., Miller, W.E., Field, M.E., Pierce, K.L., and Lefkowitz, R.J.. (2001). "Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds". Proc. Natl. Acad. Sci., USA 98 (5): 2449–2454. DOI:10.1073/pnas.041604898. PMID 11226259.
  • Wei, H., Ahn, S., Shenoy, S.K., Karnik, S.S., Hunyady, L., Luttrell, L.M. and Lefkowitz, R.J.. (2003). "Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2". Proc. Natl. Acad. Sci. USA 100 (19): 10782–10787. DOI:10.1073/pnas.1834556100. PMID 12949261.
  • Ahn, S., Shenoy, S.K. Wei, H. and Lefkowitz, R.J.. (2004). "Differential kinetic and spatial patterns of β-arrestin2 and G protein-mediated ERK activated by the angiotensin II receptor". J. Biol. Chem. 279 (34): 35518–35525. DOI:10.1074/jbc.M405878200. PMID 15205453.
  • Lefkowitz, R.J. and Shenoy, S.K.. (2005). "Transduction of Receptor Signals by β-arrestins". Science.USA 308 (5721): 512–517. DOI:10.1126/science.1109237. PMID 15845844.
  • Shenoy, S.K., Drake, M.T., Nelson, C.D., Houtz, D.A., Xiao, K., Madabushi, S., Reiter, E., Premont, R.T., Lichtarge, O. and Lefkowitz, R.J.. (2006). "β-arrestin-dependent G Protein-independent ERK 1/2 Activation by the β2-adrenergic receptor". J. Biol. Chem. 281 (2): 1261–1273. DOI:10.1074/jbc.M506576200. PMID 16280323.
  • Rajagopal, S., Rajagopal, K., Lefkowitz, R.J.. (2010). "Teaching Old receptors new tricks: biasing seven-transmembrane receptors". Nature Reviews Drug Discovery. USA 9 (5): 1–12. DOI:10.1038/nrd3091. PMID 20431569.

Referências

Ligações externas[editar | editar código-fonte]


Precedido por
Dan Shechtman
Nobel de Química
2012
com Brian Kobilka
Sucedido por
Martin Karplus, Michael Levitt e Arieh Warshel


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