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  • 1
    Electronic Resource
    Electronic Resource
    Regulation of MC1R signalling by G-protein-coupled receptor kinases (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Experimental dermatology 13 (2004), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0906-6705.2004.00212f.x
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  • 2
    Electronic Resource
    Electronic Resource
    Partial characterization of IR-α-MSH peptides found in melanoma tumors
    Amsterdam : Elsevier
    Peptides 13 (1992), S. 989-994 
    Details
    ISSN: 0196-9781
    Keywords: Melanocyte ; Melanoma ; Melanotropin ; POMC ; α-MSH
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0196-9781(92)90060-G
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Proteolysis with trypsin of mammalian tyrosinase isoforms from B16 mouse melanoma
    Amsterdam : Elsevier
    Archives of Biochemistry and Biophysics 297 (1992), S. 221-227 
    Details
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0003-9861(92)90665-J
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  • 4
    Electronic Resource
    Electronic Resource
    Agonist-independent, high constitutive activity of the human mela-nocortin 1 receptor (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc
    Experimental dermatology 13 (2004), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The melanocortin hormones act on epidermal melanocytes to increase eumelanogenesis, melanocyte dendricity and likely melanosome transfer to keratinocytes. These actions are mediated by the melanocortin 1 receptor (MC1R), positively coupled to adenylyl cyclase. Gain-of-function Mc1r alleles are associated with dark, eumelanic skin. Conversely, loss-of-function variants or overexpression of agouti, the natural antagonist, yield yellow, pheomelanic furs. In humans, loss-of-function MC1R variants are associated with fair skin, poor tanning and increased skin cancer risk. Therefore, MC1R is a key regulator of mammalian pigmentation. An induction of constitutive pigmentation in amelanotic mouse melanoma cells following the expression of MC1R has been reported, suggesting that this receptor might display agonist-independent activity, although this aspect has not yet been comparatively studied for MC1R and Mc1r. We show that the expression of MC1R in heterologous systems leads to high agonist-independent increases in intracellular cAMP. This basal signalling is a function of the quantity of receptor expressed, is considerably higher for MC1R than Mc1r and is also observed in human melanoma cells overexpressing MC1R. Moreover, MC1R basal signalling is abolished or reduced by point mutations impairing the response to agonists. Lastly, the expression of wild-type MC1R, but not of loss-of-function mutants potently stimulates forskolin activation of adenylyl cyclase, a feature characteristic of constitutively active G-coupled receptors. Therefore, we conclude that MC1R displays a strong agonist-independent constitutive activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0906-6705.2004.212bb.x
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  • 5
    Electronic Resource
    Electronic Resource
    Selective labeling of α-bungarotoxin with fluorescein isothiocyanate and its use for the study of toxin-acetylcholine receptor interactions (1990)
    Springer
    The protein journal 9 (1990), S. 683-693 
    Details
    ISSN: 1573-4943
    Keywords: Acetylcholine receptor ; α-bungarotoxin ; fluorescent labels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The main product of the reaction of fluorescein isothiocyanate (FITC) and bungarotoxin (Bgt) under near stoichiometric conditions is a monofluorescein derivative preferentially labeled at Lys 26, a highly conserved residue known to be involved in the binding (McDaniel, C. S., Manshouri, T., and Atassi, M. Z. (1987)J. Prot. Chem. 6, 455–461; Garcia-Borron, J. C., Bieber, A. L., and Martinez-Carrion, M. (1987)Biochemistry 26, 4295–4303) of postsynaptic neurotoxins specific for the nicotinic acetylcholine receptor (AcChR). The fluorescently labeled toxin retains a high affinity for the AcChR, and an unaltered specificity. Binding of FITC-Bgt to AcChR results in a significant decrease in the fluorescence intensity of the probe. This AcChR-mediated quenching of FITC-Bgt fluorescence allows for a continuous monitoring of the binding process. The quenching of free and bound FITC-Bgt by charged and neutral quenchers shows few fluorophore accessibility changes as induced by the toxin-bound state. The results are consistent with a model in which the positively charged concave surface of the toxin interacts with a negatively charged complementary surface in the receptor molecule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01024763
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    Paper (German National Licenses)
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