Molecular Cloning of a Novel Human Melanocortin Receptor

Chhajlani, Vijay; Muceniece, Ruta; Wikberg, Jarl E. S.

doi:10.1006/bbrc.1993.2125

Cited by 307 publications

(174 citation statements)

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“…All procedures were performed according to previously described methods (Chhajlani et al, 1993). Briefly, 2610 6 cells were collected and washed with PBS, acidic glycine buffer and RPMI medium.…”

Section: Mc1 Receptor Binding Studiesmentioning

confidence: 99%

“…POMC derived peptides have been shown to transmit their signal via G-protein coupled receptors through the formation of cyclic AMP and activation of protein kinase C (Friedmann et al, 1990;Ao et al, 1998;AbdelMalek et al, 2000). Five different subtypes of melanocortin receptors with different tissue distribution have been described (Chhajlani and Wikberg, 1992;Mountjoy et al, 1992;Chhajlani et al, 1993;Gantz et al, 1993a,b). Of these, the melanocortin 1 receptor (MC1R) was originally described to be mainly located on melanoma and melanocytes (Varga et al, 1976;Tatro et al, 1990;Chhajlani, 1996;Suzuki et al, 1996;Xia et al, 1996).…”

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confidence: 99%

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Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Salazar‐Onfray

López

Lundqvist³

et al. 2002

Br J Cancer

106

111

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The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT -PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a 'therapeutic window' to be exploited in cancer immunotherapy.

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Section: Mc1 Receptor Binding Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Salazar‐Onfray

López

Lundqvist³

et al. 2002

Br J Cancer

106

111

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“…There are five known melanocortin receptor (MCR) subtypes, all of which belong to the family of seven transmembrane G-protein coupled receptors (GPCRs), and whose activation is linked to the generation of intracellular cAMP [3,7,8,12,[14][15][16]22,31,34,38]. Importantly, the interaction of the melanocortin peptides with their receptors can be modified by two endogenous protein antagonists, agouti, and agouti-related protein, which are the products of two distinct genes [33,35].…”

Section: Introductionmentioning

confidence: 99%

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

et al. 2006

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“…To date, five melanocortin receptor (MC-R) subtypes have been identified [3,[7][8][9][12][13][14][15][24][25][26]30]. Three of these, MC3-R, MC4-R and MC~-R are expressed in the nervous system.…”

Section: Introductionmentioning

confidence: 99%

Melanocortin receptors mediate α-MSH-induced stimulation of neurite outgrowth in neuro 2A cells

Adan

Kraan

Doornbos

et al. 1996

Molecular Brain Research

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Melanocortins (MC), neuropeptides derived from pro-opiomelanocortin, have been implicated in enhancing neurite outgrowth via an as yet unknown mechanism. Recently, five MC receptors have been identified, three of which, the MC3-R, the MC4-R and the MCs-R, are expressed in the nervous system. In this study, a-MSH and the melanocortin analog [D-PheT]ACTH (4-10) were able to stimulate neurite outgrowth in the neuroblastoma cell line Neuro 2A. ACTH (4-10), -/2-MSH and ORG2766 were inactive. In addition, the MCa-R antagonist [D-Arg8]ACTH (4-10), inhibited the a-MSH effect, indicating that the MCa-R mediated stimulation of neurite outgrowth by o~-MSH. Indeed, the presence of MCa-R mRNA in Neuro 2A cells was demonstrated by a RNase protection assay. Heterologous expression of the MCs-R in Neuro 2A cells lead to the recruitment of a responsiveness to -/2-MSH, but did not increase the effect of a-MSH on neurite outgrowth. This finding indicated that the function of MC4-R can also be exerted by another MC receptor, suggesting that the coupling to G,, which they have in common, plays an essential role in the neurite outgrowth promoting effect. This was further substantiated by the fact that forskolin treatment per se induced neurite outgrowth in a similar fashion. These data imply that the neurotrophic properties of a-MSH are likely to result from G~-coupled MC receptor activity in neuronal cells.

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Molecular Cloning of a Novel Human Melanocortin Receptor

Cited by 307 publications

References 0 publications

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

Melanocortin receptors mediate α-MSH-induced stimulation of neurite outgrowth in neuro 2A cells

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