Regulation of MC1R signalling by G‐protein‐coupled receptor kinases
Identifieur interne : 000683 ( Istex/Corpus ); précédent : 000682; suivant : 000684Regulation of MC1R signalling by G‐protein‐coupled receptor kinases
Auteurs : J. C. García-Borr NSource :
- Experimental Dermatology [ 0906-6705 ] ; 2004-09.
English descriptors
- Teeft :
- 2department, 3department, Acth, Activates, Adhesion, Adrenomedullin, Agonist, Allergic dermatitis, Anagen, Antimicrobial, Antioxidant, Apoptosis, Apoptotic, Atopic, Atopic dermatitis, Autoimmune, Basal, Bdnf, Biomedical, Biomedical sciences, Bmdcs, Bohm1, Boltzmann, Calcitonin, Calcitonin peptide, Capsaicin, Cell biology, Cgrp, Charite, Costimulatory molecules, Cutaneous, Cutaneous inflammation, Cytokine, Cytotoxicity, Dendricity, Dendritic, Dendritic cells, Dermal, Dermal microvascular, Dermatitis, Dermatology, Endocrine, Endogenous, Endothelial, Endothelial cells, Eosinophil, Epidermal, Epithelial, Extracellular, Fibre, Fibroblast, Follicle, Functional role, Glutamine, Hacat, Hacat cells, Hair follicle, Hair follicles, Hair growth, Hamburg, Hdmec, Healthy subjects, Homeostasis, Human hair follicle, Human sebocytes, Human skin, Hyperalgesia, Immune, Immune cells, Immune response, Immune system, Immunobiology, Immunohistochemistry, Immunomodulatory, Immunoreactivity, Important role, Inflammation, Inflammatory, Insr, Internal medicine, Intracellular, Intracellular calcium concentration, Keratinocyte, Keratinocytes, Kinase, Ligand, Ludwig boltzmann institute, Luger1, Lymphocyte, Mast cells, Mc1r, Mediator, Melanin, Melanocortin, Melanocortin receptors, Melanocyte, Melanogenesis, Melanoma, Melanoma cells, Melatonin, Microvascular, Mitf, Modulators, Mrna, Msc, Munster, Murine, Naltrexone, Nerve fibers, Nerve fibres, Nerve growth factor, Nervous system, Neuroendocrine, Neurogenic, Neurogenic inflammation, Neuron, Neuropeptide, Neuropeptides, Neurotrophic, Neurotrophic factor, Neurotrophin, Neurotrophins, Neutral endopeptidase, Nk1r, Nmda, Pacap, Papilla, Par2, Pathway, Peptide, Peripheral blood eosinophils, Pigmentation, Plasma membrane, Pomc, Pomc peptides, Present study, Proinflammatory, Pruritus, Receptor, Regulator, Rheumatoid arthritis, Schwann, Sebaceous, Sebaceous gland, Sebocytes, Sensitization, Sensory nerves, Sensory neurons, Somatostatin, Trafficking, Transgenic, Transgenic mice, Trpv1, Tumour, Upregulated, Upregulation, Uremic pruritus, Urocortin, Vanilloid, Vasoactive, Vellus hair follicles, Wound healing.
Abstract
The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation.
Url:
DOI: 10.1111/j.0906-6705.2004.00212f.x
Links to Exploration step
ISTEX:4139881425E46EEA8FC6D1946AFE9E987FC56FA7Le document en format XML
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cells</term><term>Dermal</term><term>Dermal microvascular</term><term>Dermatitis</term><term>Dermatology</term><term>Endocrine</term><term>Endogenous</term><term>Endothelial</term><term>Endothelial cells</term><term>Eosinophil</term><term>Epidermal</term><term>Epithelial</term><term>Extracellular</term><term>Fibre</term><term>Fibroblast</term><term>Follicle</term><term>Functional role</term><term>Glutamine</term><term>Hacat</term><term>Hacat cells</term><term>Hair follicle</term><term>Hair follicles</term><term>Hair growth</term><term>Hamburg</term><term>Hdmec</term><term>Healthy subjects</term><term>Homeostasis</term><term>Human hair follicle</term><term>Human sebocytes</term><term>Human skin</term><term>Hyperalgesia</term><term>Immune</term><term>Immune cells</term><term>Immune response</term><term>Immune system</term><term>Immunobiology</term><term>Immunohistochemistry</term><term>Immunomodulatory</term><term>Immunoreactivity</term><term>Important role</term><term>Inflammation</term><term>Inflammatory</term><term>Insr</term><term>Internal medicine</term><term>Intracellular</term><term>Intracellular calcium concentration</term><term>Keratinocyte</term><term>Keratinocytes</term><term>Kinase</term><term>Ligand</term><term>Ludwig boltzmann institute</term><term>Luger1</term><term>Lymphocyte</term><term>Mast cells</term><term>Mc1r</term><term>Mediator</term><term>Melanin</term><term>Melanocortin</term><term>Melanocortin receptors</term><term>Melanocyte</term><term>Melanogenesis</term><term>Melanoma</term><term>Melanoma cells</term><term>Melatonin</term><term>Microvascular</term><term>Mitf</term><term>Modulators</term><term>Mrna</term><term>Msc</term><term>Munster</term><term>Murine</term><term>Naltrexone</term><term>Nerve fibers</term><term>Nerve fibres</term><term>Nerve growth factor</term><term>Nervous system</term><term>Neuroendocrine</term><term>Neurogenic</term><term>Neurogenic 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mice</term><term>Trpv1</term><term>Tumour</term><term>Upregulated</term><term>Upregulation</term><term>Uremic pruritus</term><term>Urocortin</term><term>Vanilloid</term><term>Vasoactive</term><term>Vellus hair follicles</term><term>Wound healing</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>receptor</json:string><json:string>dermatology</json:string><json:string>follicle</json:string><json:string>keratinocytes</json:string><json:string>cutaneous</json:string><json:string>melanocyte</json:string><json:string>fibroblast</json:string><json:string>peptide</json:string><json:string>munster</json:string><json:string>mc1r</json:string><json:string>immune</json:string><json:string>pathway</json:string><json:string>inflammation</json:string><json:string>neuropeptides</json:string><json:string>melanoma</json:string><json:string>cgrp</json:string><json:string>epidermal</json:string><json:string>neurogenic</json:string><json:string>pomc</json:string><json:string>agonist</json:string><json:string>bdnf</json:string><json:string>dermatitis</json:string><json:string>2department</json:string><json:string>neuropeptide</json:string><json:string>dermal</json:string><json:string>capsaicin</json:string><json:string>pruritus</json:string><json:string>fibre</json:string><json:string>human 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epidermis</json:string><json:string>university medicine berlin</json:string><json:string>neuropeptide substance</json:string><json:string>hair loss</json:string><json:string>contact hypersensitivity</json:string><json:string>humboldt university</json:string><json:string>sigma receptors</json:string><json:string>high concentrations</json:string><json:string>human fibroblasts</json:string><json:string>hair follicle growth</json:string><json:string>hair fibre elongation</json:string><json:string>hair manner</json:string><json:string>western blot</json:string><json:string>capsaicin cytotoxicity</json:string><json:string>human terminal</json:string><json:string>receptor system</json:string><json:string>mrna expression</json:string><json:string>avena rhealba1</json:string><json:string>morphine modulation</json:string><json:string>urocortin peptides</json:string><json:string>cutaneous neurogenic inflammation</json:string><json:string>other hand</json:string><json:string>several neuropeptides</json:string><json:string>skin inflammation</json:string><json:string>dermal fibroblasts</json:string><json:string>inhibitor</json:string><json:string>activation</json:string><json:string>antagonist</json:string><json:string>mast</json:string><json:string>molecule</json:string><json:string>cell</json:string><json:string>cultured</json:string><json:string>vivo</json:string><json:string>skin</json:string><json:string>nerve</json:string></teeft></keywords><author><json:item><name>J. C. García‐Borrón</name><affiliations><json:string>Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain</json:string></affiliations></json:item></author><articleId><json:string>EXD212F</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>abstract</json:string></originalGenre><abstract>The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation.</abstract><qualityIndicators><score>7.736</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595 x 782 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractCharCount>1561</abstractCharCount><pdfWordCount>23570</pdfWordCount><pdfCharCount>158516</pdfCharCount><pdfPageCount>25</pdfPageCount><abstractWordCount>228</abstractWordCount></qualityIndicators><title>Regulation of MC1R signalling by G‐protein‐coupled receptor kinases</title><genre><json:string>abstract</json:string></genre><host><title>Experimental Dermatology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1600-0625</json:string></doi><issn><json:string>0906-6705</json:string></issn><eissn><json:string>1600-0625</json:string></eissn><publisherId><json:string>EXD</json:string></publisherId><volume>13</volume><issue>9</issue><pages><first>568</first><last>568</last><total>1</total></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>science</json:string><json:string>dermatology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>dermatology & venereal diseases</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string><json:string>cardiologie. appareil circulatoire</json:string></inist></categories><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1111/j.0906-6705.2004.00212f.x</json:string></doi><id>4139881425E46EEA8FC6D1946AFE9E987FC56FA7</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/4139881425E46EEA8FC6D1946AFE9E987FC56FA7/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/4139881425E46EEA8FC6D1946AFE9E987FC56FA7/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/4139881425E46EEA8FC6D1946AFE9E987FC56FA7/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Regulation of MC1R signalling by G‐protein‐coupled receptor kinases</title><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd/Inc.</publisher><pubPlace>Oxford, UK; Malden, USA</pubPlace><availability><p>WILEY</p></availability><date>2004</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Regulation of MC1R signalling by G‐protein‐coupled receptor kinases</title><author xml:id="author-1"><persName><forename type="first">J. C.</forename><surname>García‐Borrón</surname></persName><affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain</affiliation></author></analytic><monogr><title level="j">Experimental Dermatology</title><idno type="pISSN">0906-6705</idno><idno type="eISSN">1600-0625</idno><idno type="DOI">10.1111/(ISSN)1600-0625</idno><imprint><publisher>Blackwell Publishing Ltd/Inc.</publisher><pubPlace>Oxford, UK; Malden, USA</pubPlace><date type="published" when="2004-09"></date><biblScope unit="volume">13</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="568">568</biblScope><biblScope unit="page" to="568">568</biblScope></imprint></monogr><idno type="istex">4139881425E46EEA8FC6D1946AFE9E987FC56FA7</idno><idno type="DOI">10.1111/j.0906-6705.2004.00212f.x</idno><idno type="ArticleID">EXD212F</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. 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C.</givenNames><familyName>García‐Borrón</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="ES"><unparsedAffiliation><b>Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain</b></unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><p>The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of <i>MC1R</i> gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. 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C.</namePart><namePart type="family">García‐Borrón</namePart><affiliation>Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="abstract" displayLabel="abstract"></genre><originInfo><publisher>Blackwell Publishing Ltd/Inc.</publisher><place><placeTerm type="text">Oxford, UK; Malden, USA</placeTerm></place><dateIssued encoding="w3cdtf">2004-09</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="words">2708</extent></physicalDescription><abstract lang="en">The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist‐dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist‐dependent signalling, and 8) cAMP production in agonist‐stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation.</abstract><relatedItem type="host"><titleInfo><title>Experimental Dermatology</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0906-6705</identifier><identifier type="eISSN">1600-0625</identifier><identifier type="DOI">10.1111/(ISSN)1600-0625</identifier><identifier type="PublisherID">EXD</identifier><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>13</number></detail><detail type="issue"><caption>no.</caption><number>9</number></detail><extent unit="pages"><start>568</start><end>568</end><total>1</total></extent></part></relatedItem><identifier type="istex">4139881425E46EEA8FC6D1946AFE9E987FC56FA7</identifier><identifier type="DOI">10.1111/j.0906-6705.2004.00212f.x</identifier><identifier type="ArticleID">EXD212F</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd/Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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