Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy (397 views)
Gene (ISSN: 0378-1119), 2010 Jun 1; 457(1-2): 35-41.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.266, 5-year impact factor: 2.61
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-77951935284&partnerID=40&md5=2ef0d08518837a7e477974e56b94d106
Keywords: Confocal Microscopy, Dominant Negative, Functional Analysis, Homology Modeling, Mc4r Mutants, Severe Obesity, Melanocortin 4 Receptor, Alpha Intermedin, Ligand, Mc4r Protein, Human, Mitogen Activated Protein Kinase 1, Mutant Protein, Adult, Amino Acid Substitution, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Cell Membrane, Cell Mutant, Cellular Distribution, Child, Controlled Study, Disease Severity, Endoplasmic Reticulum, Gene Identification, Genetic Association, Heterozygosity, Homeostasis, Homozygosity, Human Cell, Italy, Ligand Binding, Major Clinical Study, Missense Mutation, Priority Journal, Protein Analysis, Protein Function, Signal Transduction, Structural Homology, Structure Analysis, Wild Type, Cell Culture, Chemical Structure, Drug Effect, Genetic Transfection, Metabolism, Morbid Obesity, Phosphorylation, Physiology, Protein Binding, Structure Activity Relation, Tissue Distribution, Alpha-Msh, Mitogen-Activated Protein Kinase 1, Molecular, Structure-Activity Relationship,
Affiliations:
*** IBB - CNR ***
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Facoltà di Scienze Motorie, Università Parthenope, Naples, Italy
Istituto di Ricovero e Cura a carattere scientifico, Fondazione SDN, Naples, Italy
Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Biostrutture e Bioimmagini, Naples, Italy
Dipartimento Scienze per la Salute, Università del Molise, Campobasso, Italy
CEINGE-Biotecnologie Avanzate s.ca.r.l., Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Naples, Italy
References:
Adachi, S., Nakano, T., Vliagoftis, H., Dean, D., Metcalfe, D.D., Receptor-mediated modulation of murine mast cell function by a-melanocyte stimulating hormone (1999) J. Immunol., 163, pp. 3363-336
Adan, R.A., Gispen, W.H., Brain melanocortin receptors: from cloning to function (1997) Peptides, 18, pp. 1279-1287
Buono, P., Cassano, S., Alfieri, A., Mancini, A., Salvatore, F., Human aldolase C gene expression is regulated by adenosine 3', 5'-cyclic monophosphate (cAMP) in PC12 cells (2002) Gene, 291, pp. 115-121
Buono, P., Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy (2005) Clin. Chem., 51, pp. 1358-1364
Cherezov, V., High-resolution crystal structure of an engineered human βf2-adrenergic G protein-coupled receptor (2007) Science, 318, pp. 1258-1265
Cole, L., Davies, D., Hyde, G.J., Ashford, A.E., ER-Tracker dye and BODIPY-brefeldin A differentiate the endoplasmic reticulum and golgi bodies from the tubular-vacuole system in living hyphae of Pisolithus tinctorius (2000) J. Microsc., 197, pp. 239-249
Daniels, D., Patten, C.S., Roth, J.D., Yee, D.K., Fluharty, S.J., Melanocortin receptor signaling kinase in vitro and through mitogen-activated protein in rat hypothalamus (2003) Brain Res., 986, pp. 1-11
Dubern, B., Homozygous null mutation of the melanocortin-4 receptor and severe early-onset obesity (2007) J. Pediatr., 150, pp. 613-617
Fan, Z.C., Tao, Y.X., Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients (2009) J. Cell. Mol. Med., , Electronic publication ahead of print
Farooqi, I.S., Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency (2000) J. Clin. Invest., 106, pp. 271-279
Farooqi, I.S., Keogh, J.M., Yeo, G.S., Lank, E.J., Cheetham, T., O'Rahilly, S., Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene (2003) N. Engl. J. Med., 348, pp. 1085-1095
Gantz, I., Molecular cloning, expression, and gene localization of a fourth melanocortin receptor (1993) J. Biol. Chem., 268, pp. 15174-15179
Govaerts, C., Obesity-associated mutations in the melanocortin 4 receptor provide novel insights into its function (2005) Peptides, 26, pp. 1909-1919
Gu, W., Identification and functional analysis of novel human melanocortin-4 receptor variants (1999) Diabetes, 48, pp. 635-639
Hinney, A., Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans (1999) J. Clin. Endocrinol. Metab., 84, pp. 1483-1486
Hinney, A., Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity (2003) J. Clin. Endocrinol. Metab., 88, pp. 4258-4267
Ho, G., MacKenzie, R.G., Functional characterization of mutations in melanocortin-4 receptor associated with human obesity (1999) J. Biol. Chem., 274, pp. 35816-35822
Huszar, D., Targeted disruption of the melanocortin-4 receptor results in obesity in mice (1997) Cell, 88, pp. 131-141
Jones, E.Y., Walker, N.P., Stuart, D.I., Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry (1991) Acta Crystallogr. A, 47, pp. 753-770
Kraulis, P.J., Similarity of protein G and ubiquitin (1991) Science, 254, pp. 581-582
Lubrano-Berthelier, C., Molecular genetics of human obesity-associated MC4R mutations (2003) Ann. N. Y. Acad. Sci., 994, pp. 49-57
Luttrell, L.M., Activation and targeting of mitogen-activated protein kinases by G-protein-coupled receptors (2002) Can. J. Physiol. Pharmacol., 80, pp. 375-382
Luttrell, L.M., van Biesen, T., Hawes, B.E., Koch, W.J., Krueger, K.M., Touhara, K., G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors (1997) Adv. Second Messenger Phosphoprotein Res., 31, pp. 263-277
MacKenzie, R.G., Obesity-associated mutations in the human melanocortin-4 receptor gene (2006) Peptides, 27, pp. 395-403
Mergen, M., Mergen, H., Ozata, M., Oner, R., Oner, C., A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity (2001) J. Clin. Endocrinol. Metab., 86, pp. 3448-3451
Merritt, E.A., Bacon, D.J., Raster3D: photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Miraglia Del Giudice, E., Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity (2002) Int. J. Obes. Relat. Metab. Disord., 26, pp. 647-651
Nijenhuis, W.A., Garner, K.M., van Rozen, R.J., Adan, R.A., Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity (2003) J. Biol. Chem., 278, pp. 22939-22945
Paemeleire, K., Intercellular calcium waves in HeLa cells expressing GFP-labeled connexin 43, 32, or 26 (2000) Mol. Biol. Cell, 11, pp. 1815-1827
Palczewski, K., Crystal structure of rhodopsin: a G protein-coupled receptor (2000) Science, 289, pp. 739-745
Patten, C.S., Daniels, D., Suzuki, A., Fluharty, S.J., Yee, D.K., Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation (2007) Regul. Pept., 142, pp. 111-122
Pogozheva, I.D., Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists (2005) Biochemistry, 44, pp. 11329-11341
Santoro, N., Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity (2009) BMC Med. Genet., 10, p. 25. , Mar 12
Schwartz, M.W., Woods, S.C., Porte, D., Seeley, R.J., Baskin, D.G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671
Sina, M., Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene (1999) Am. J. Hum. Genet., 65, pp. 1501-1507
Srinivasan, S., Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans (2004) J. Clin. Invest., 114, pp. 1158-1164
Tan, K., Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor (2009) Endocrinology, 150, pp. 114-125
Vaisse, C., Clement, K., Guy-Grand, B., Froguel, P., A frameshift mutation in human MC4R is associated with a dominant form of obesity (1998) Nat. Genet., 20, pp. 113-114
Vongs, A., Lynn, N.M., Charles, R.I., Activation of MAP kinase by MC4-R through PI3 kinase (2004) Regul. Pept., 120, pp. 113-118
Wangensteen, T., Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in Norway (2009) Exp. Clin. Endocrinol. Diabetes, 117 (6), pp. 266-273
Warne, A., Structure of the beta1-adrenergic G protein coupled receptor (2008) Nature, 454, pp. 486-491
Wilczynski, A., Identification of putative agouti-related protein (87-132)-melanocortin-4 receptor interactions by homology molecular modeling and validation using chimeric peptide ligands (2004) J. Med. Chem., 47, pp. 2194-2207
Yeo, G.S., Farooqi, I.S., Aminian, S., Halsall, D.J., Stanhope, R.G., O'Rahilly, S., A frameshift mutation in MC4R associated with dominantly inherited human obesity (1998) Nat. Genet., 20, pp. 111-112
Adan, R. A., Gispen, W. H., Brain melanocortin receptors: from cloning to function (1997) Peptides, 18, pp. 1279-1287
Fan, Z. C., Tao, Y. X., Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients (2009) J. Cell. Mol. Med., , Electronic publication ahead of print
Farooqi, I. S., Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency (2000) J. Clin. Invest., 106, pp. 271-279
Farooqi, I. S., Keogh, J. M., Yeo, G. S., Lank, E. J., Cheetham, T., O'Rahilly, S., Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene (2003) N. Engl. J. Med., 348, pp. 1085-1095
Jones, E. Y., Walker, N. P., Stuart, D. I., Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry (1991) Acta Crystallogr. A, 47, pp. 753-770
Kraulis, P. J., Similarity of protein G and ubiquitin (1991) Science, 254, pp. 581-582
Luttrell, L. M., Activation and targeting of mitogen-activated protein kinases by G-protein-coupled receptors (2002) Can. J. Physiol. Pharmacol., 80, pp. 375-382
Luttrell, L. M., van Biesen, T., Hawes, B. E., Koch, W. J., Krueger, K. M., Touhara, K., G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors (1997) Adv. Second Messenger Phosphoprotein Res., 31, pp. 263-277
MacKenzie, R. G., Obesity-associated mutations in the human melanocortin-4 receptor gene (2006) Peptides, 27, pp. 395-403
Merritt, E. A., Bacon, D. J., Raster3D: photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Nijenhuis, W. A., Garner, K. M., van Rozen, R. J., Adan, R. A., Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity (2003) J. Biol. Chem., 278, pp. 22939-22945
Patten, C. S., Daniels, D., Suzuki, A., Fluharty, S. J., Yee, D. K., Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation (2007) Regul. Pept., 142, pp. 111-122
Pogozheva, I. D., Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists (2005) Biochemistry, 44, pp. 11329-11341
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., Baskin, D. G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671
Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., O'Rahilly, S., A frameshift mutation in MC4R associated with dominantly inherited human obesity (1998) Nat. Genet., 20, pp. 111-112
Gene (ISSN: 0378-1119), 2010 Jun 1; 457(1-2): 35-41.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.266, 5-year impact factor: 2.61
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-77951935284&partnerID=40&md5=2ef0d08518837a7e477974e56b94d106
Keywords: Confocal Microscopy, Dominant Negative, Functional Analysis, Homology Modeling, Mc4r Mutants, Severe Obesity, Melanocortin 4 Receptor, Alpha Intermedin, Ligand, Mc4r Protein, Human, Mitogen Activated Protein Kinase 1, Mutant Protein, Adult, Amino Acid Substitution, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Cell Membrane, Cell Mutant, Cellular Distribution, Child, Controlled Study, Disease Severity, Endoplasmic Reticulum, Gene Identification, Genetic Association, Heterozygosity, Homeostasis, Homozygosity, Human Cell, Italy, Ligand Binding, Major Clinical Study, Missense Mutation, Priority Journal, Protein Analysis, Protein Function, Signal Transduction, Structural Homology, Structure Analysis, Wild Type, Cell Culture, Chemical Structure, Drug Effect, Genetic Transfection, Metabolism, Morbid Obesity, Phosphorylation, Physiology, Protein Binding, Structure Activity Relation, Tissue Distribution, Alpha-Msh, Mitogen-Activated Protein Kinase 1, Molecular, Structure-Activity Relationship,
Affiliations:
*** IBB - CNR ***
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Facoltà di Scienze Motorie, Università Parthenope, Naples, Italy
Istituto di Ricovero e Cura a carattere scientifico, Fondazione SDN, Naples, Italy
Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore, Università di Napoli Federico II, Naples, Italy
CNR Istituto di Biostrutture e Bioimmagini, Naples, Italy
Dipartimento Scienze per la Salute, Università del Molise, Campobasso, Italy
CEINGE-Biotecnologie Avanzate s.ca.r.l., Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Naples, Italy
References:
Adachi, S., Nakano, T., Vliagoftis, H., Dean, D., Metcalfe, D.D., Receptor-mediated modulation of murine mast cell function by a-melanocyte stimulating hormone (1999) J. Immunol., 163, pp. 3363-336
Adan, R.A., Gispen, W.H., Brain melanocortin receptors: from cloning to function (1997) Peptides, 18, pp. 1279-1287
Buono, P., Cassano, S., Alfieri, A., Mancini, A., Salvatore, F., Human aldolase C gene expression is regulated by adenosine 3', 5'-cyclic monophosphate (cAMP) in PC12 cells (2002) Gene, 291, pp. 115-121
Buono, P., Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy (2005) Clin. Chem., 51, pp. 1358-1364
Cherezov, V., High-resolution crystal structure of an engineered human βf2-adrenergic G protein-coupled receptor (2007) Science, 318, pp. 1258-1265
Cole, L., Davies, D., Hyde, G.J., Ashford, A.E., ER-Tracker dye and BODIPY-brefeldin A differentiate the endoplasmic reticulum and golgi bodies from the tubular-vacuole system in living hyphae of Pisolithus tinctorius (2000) J. Microsc., 197, pp. 239-249
Daniels, D., Patten, C.S., Roth, J.D., Yee, D.K., Fluharty, S.J., Melanocortin receptor signaling kinase in vitro and through mitogen-activated protein in rat hypothalamus (2003) Brain Res., 986, pp. 1-11
Dubern, B., Homozygous null mutation of the melanocortin-4 receptor and severe early-onset obesity (2007) J. Pediatr., 150, pp. 613-617
Fan, Z.C., Tao, Y.X., Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients (2009) J. Cell. Mol. Med., , Electronic publication ahead of print
Farooqi, I.S., Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency (2000) J. Clin. Invest., 106, pp. 271-279
Farooqi, I.S., Keogh, J.M., Yeo, G.S., Lank, E.J., Cheetham, T., O'Rahilly, S., Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene (2003) N. Engl. J. Med., 348, pp. 1085-1095
Gantz, I., Molecular cloning, expression, and gene localization of a fourth melanocortin receptor (1993) J. Biol. Chem., 268, pp. 15174-15179
Govaerts, C., Obesity-associated mutations in the melanocortin 4 receptor provide novel insights into its function (2005) Peptides, 26, pp. 1909-1919
Gu, W., Identification and functional analysis of novel human melanocortin-4 receptor variants (1999) Diabetes, 48, pp. 635-639
Hinney, A., Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans (1999) J. Clin. Endocrinol. Metab., 84, pp. 1483-1486
Hinney, A., Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity (2003) J. Clin. Endocrinol. Metab., 88, pp. 4258-4267
Ho, G., MacKenzie, R.G., Functional characterization of mutations in melanocortin-4 receptor associated with human obesity (1999) J. Biol. Chem., 274, pp. 35816-35822
Huszar, D., Targeted disruption of the melanocortin-4 receptor results in obesity in mice (1997) Cell, 88, pp. 131-141
Jones, E.Y., Walker, N.P., Stuart, D.I., Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry (1991) Acta Crystallogr. A, 47, pp. 753-770
Kraulis, P.J., Similarity of protein G and ubiquitin (1991) Science, 254, pp. 581-582
Lubrano-Berthelier, C., Molecular genetics of human obesity-associated MC4R mutations (2003) Ann. N. Y. Acad. Sci., 994, pp. 49-57
Luttrell, L.M., Activation and targeting of mitogen-activated protein kinases by G-protein-coupled receptors (2002) Can. J. Physiol. Pharmacol., 80, pp. 375-382
Luttrell, L.M., van Biesen, T., Hawes, B.E., Koch, W.J., Krueger, K.M., Touhara, K., G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors (1997) Adv. Second Messenger Phosphoprotein Res., 31, pp. 263-277
MacKenzie, R.G., Obesity-associated mutations in the human melanocortin-4 receptor gene (2006) Peptides, 27, pp. 395-403
Mergen, M., Mergen, H., Ozata, M., Oner, R., Oner, C., A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity (2001) J. Clin. Endocrinol. Metab., 86, pp. 3448-3451
Merritt, E.A., Bacon, D.J., Raster3D: photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Miraglia Del Giudice, E., Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity (2002) Int. J. Obes. Relat. Metab. Disord., 26, pp. 647-651
Nijenhuis, W.A., Garner, K.M., van Rozen, R.J., Adan, R.A., Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity (2003) J. Biol. Chem., 278, pp. 22939-22945
Paemeleire, K., Intercellular calcium waves in HeLa cells expressing GFP-labeled connexin 43, 32, or 26 (2000) Mol. Biol. Cell, 11, pp. 1815-1827
Palczewski, K., Crystal structure of rhodopsin: a G protein-coupled receptor (2000) Science, 289, pp. 739-745
Patten, C.S., Daniels, D., Suzuki, A., Fluharty, S.J., Yee, D.K., Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation (2007) Regul. Pept., 142, pp. 111-122
Pogozheva, I.D., Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists (2005) Biochemistry, 44, pp. 11329-11341
Santoro, N., Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity (2009) BMC Med. Genet., 10, p. 25. , Mar 12
Schwartz, M.W., Woods, S.C., Porte, D., Seeley, R.J., Baskin, D.G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671
Sina, M., Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene (1999) Am. J. Hum. Genet., 65, pp. 1501-1507
Srinivasan, S., Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans (2004) J. Clin. Invest., 114, pp. 1158-1164
Tan, K., Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor (2009) Endocrinology, 150, pp. 114-125
Vaisse, C., Clement, K., Guy-Grand, B., Froguel, P., A frameshift mutation in human MC4R is associated with a dominant form of obesity (1998) Nat. Genet., 20, pp. 113-114
Vongs, A., Lynn, N.M., Charles, R.I., Activation of MAP kinase by MC4-R through PI3 kinase (2004) Regul. Pept., 120, pp. 113-118
Wangensteen, T., Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in Norway (2009) Exp. Clin. Endocrinol. Diabetes, 117 (6), pp. 266-273
Warne, A., Structure of the beta1-adrenergic G protein coupled receptor (2008) Nature, 454, pp. 486-491
Wilczynski, A., Identification of putative agouti-related protein (87-132)-melanocortin-4 receptor interactions by homology molecular modeling and validation using chimeric peptide ligands (2004) J. Med. Chem., 47, pp. 2194-2207
Yeo, G.S., Farooqi, I.S., Aminian, S., Halsall, D.J., Stanhope, R.G., O'Rahilly, S., A frameshift mutation in MC4R associated with dominantly inherited human obesity (1998) Nat. Genet., 20, pp. 111-112
Adan, R. A., Gispen, W. H., Brain melanocortin receptors: from cloning to function (1997) Peptides, 18, pp. 1279-1287
Fan, Z. C., Tao, Y. X., Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients (2009) J. Cell. Mol. Med., , Electronic publication ahead of print
Farooqi, I. S., Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency (2000) J. Clin. Invest., 106, pp. 271-279
Farooqi, I. S., Keogh, J. M., Yeo, G. S., Lank, E. J., Cheetham, T., O'Rahilly, S., Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene (2003) N. Engl. J. Med., 348, pp. 1085-1095
Jones, E. Y., Walker, N. P., Stuart, D. I., Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry (1991) Acta Crystallogr. A, 47, pp. 753-770
Kraulis, P. J., Similarity of protein G and ubiquitin (1991) Science, 254, pp. 581-582
Luttrell, L. M., Activation and targeting of mitogen-activated protein kinases by G-protein-coupled receptors (2002) Can. J. Physiol. Pharmacol., 80, pp. 375-382
Luttrell, L. M., van Biesen, T., Hawes, B. E., Koch, W. J., Krueger, K. M., Touhara, K., G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors (1997) Adv. Second Messenger Phosphoprotein Res., 31, pp. 263-277
MacKenzie, R. G., Obesity-associated mutations in the human melanocortin-4 receptor gene (2006) Peptides, 27, pp. 395-403
Merritt, E. A., Bacon, D. J., Raster3D: photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Nijenhuis, W. A., Garner, K. M., van Rozen, R. J., Adan, R. A., Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity (2003) J. Biol. Chem., 278, pp. 22939-22945
Patten, C. S., Daniels, D., Suzuki, A., Fluharty, S. J., Yee, D. K., Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation (2007) Regul. Pept., 142, pp. 111-122
Pogozheva, I. D., Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists (2005) Biochemistry, 44, pp. 11329-11341
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., Baskin, D. G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671
Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., O'Rahilly, S., A frameshift mutation in MC4R associated with dominantly inherited human obesity (1998) Nat. Genet., 20, pp. 111-112
Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. (C) 2010 Elsevier B.V. All rights reserved.
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. (C) 2010 Elsevier B.V. All rights reserved.
Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
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Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy
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Impact Factor: 10.558
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Daniele A, Scala I, Cardillo G, Pennino C, Ungaro C, Sibilio M, Parenti G, Esposito L, Zagari A, Andria G, Salvatore F
* Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy (423 views)
Febs Journal (ISSN: 1742-464x), 2009 Apr; 276(7): 2048-2059.
Impact Factor: 3.042
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Francalanci F, Avolio M, De Luca E, Longo DL, Menchise V, Guazzi P, Sgro F, Marino M, Goitre L, Balzac F, Trabalzini L, Retta SF
* Structural and functional differences between KRIT1A and KRIT1B isoforms: A framework for understanding CCM pathogenesis (525 views)
Exp Cell Res (ISSN: 0014-4827), 2009 Jan 15; 315(2): 285-303.
Impact Factor: 3.589
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Palmieri G, Catara G, Saviano M, Langella E, Gogliettino M, Rossi M
* First archaeal PEPB-serine protease inhibitor from sulfolobus solfataricus with noncanonical amino acid sequence in the reactive-site loop (399 views)
J Proteome Res (ISSN: 1535-3893), 2009 Jan; 8(1): 327-334.
Impact Factor: 5.132
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Pentimalli F, Palmieri D, Pacelli R, Garbi C, Cesari R, Martin E, Pierantoni GM, Chieffi P, Croce CM, Costanzo V, Fedele M, Fusco A
* HMGA1 protein is a novel target of the ATM kinase (484 views)
European Journal Of Cancer (ISSN: 0959-8049), 2008 Nov; 44(17): 2668-2679.
Impact Factor: 4.475
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Daniele A, Cardillo G, Pennino C, Carbone MT, Scognamiglio D, Esposito L, Correra A, Castaldo G, Zagari A, Salvatore F
* Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants (361 views)
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2008 Jun; 1782(6): 378-384.
Impact Factor: 2.233
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Guarnieri D, Borzacchiello A, De Capua A, Ruvo M, Netti P
* Engineering of covalently immobilized gradients of RGD peptides on hydrogel scaffolds: Effect on cell behaviour (410 views)
Macromol Sympos (ISSN: 1022-1360), 2008; 266(1): 36-40.
Impact Factor: 0
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Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, Caroli A, Tramontano A, Bonaccini C, Trojer P, Bauer I, Brosch G, Sbardella G
* Small molecule inhibitors of histone arginine methyltransferases: Homology modeling, molecular docking, binding mode analysis, and biological evaluations (980 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2007 Mar 22; 50(6): 1241-1253.
Impact Factor: 4.895
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Pedone E, D'Ambrosio K, De Simone G, Rossi M, Pedone C, Bartolucci S
* Insights on a new PDI-like family: Structural and functional analysis of a protein disulfide oxidoreductase from the bacterium Aquifex aeolicus (400 views)
J Mol Biol (ISSN: 0022-2836, 1089-8638, 1089-8638electronic), 2006 Feb 10; 356(1): 155-164.
Impact Factor: 4.89
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Esposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F
* Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance (311 views)
Febs Lett (ISSN: 0014-5793, 0014-5793print, 1873-3468electronic), 2002 Nov 6; 531(2): 152-156.
Impact Factor: 3.912
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33 Records (32 excluding Abstracts).
Total impact factor: 149.096 (145.862 excluding Abstracts).
Total 5 year impact factor: 140.133 (136.431 excluding Abstracts).
Total impact factor: 149.096 (145.862 excluding Abstracts).
Total 5 year impact factor: 140.133 (136.431 excluding Abstracts).
397 views. Last view on Sunday 09 April 2023, 22:51:01
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