Calcium Flux Assay

HTS021C - ChemiSCREEN™ Human Recombinant MC2 Melanocortin Receptor Calcium-Optimized Stable Cell Line

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HTS021C
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    The melanocortins, α-, β- and g-melanocyte-stimulating hormones (MSHs) and adrenocorticotropin (ACTH), are peptides derived from a precursor protein POMC.  The MSH peptides and ACTH bind to a family of five Class 1 Gs-coupled seven transmembrane receptors (MC1-5) and play important roles in energy balance, reproductive function, pigmentation and inflammation (Gantz and Fong, 2003). MC2, the ACTH receptor, is a member of this family but is the only one that does not bind the MSHs, it instead binds ACTH exclusively. MC2 is expressed mainly in cells of the adrenal cortex, where it signals cells in the adrenal cortex to synthesize and secrete glucocorticoids (Clark A. et al., 2006). Mutations in MC2 lead to familial glucocorticoid deficiency, or ACTH insensitivity.  Familial glucocorticoid deficiency can lead to increased pigmentation and increased longitudinal bone growth (Clark A, et al. 1993, Imamine H, et al. 2005). In addition to mutations in MC2 leading to Familial glucocorticod deficiency,  it has also been shown that mutations in a protein called MC2-R accessory protein (MRAP) also lead to this disorder (Clark A, 2005).  Expression of MC2 on the cell surface has been found to be dependent on the interaction of MC2 with MRAP.  This interaction helps to move MC2 from the endoplasmic reticulum to the cell surface.  The cloned human MC2-MRAP double stable cell line is made in the Chem-1 host, which supports high levels of recombinant MC2 expression on the cell surface and contains high levels of the endogenous promiscuous G protein Gα15 to couple the receptor to the calcium signaling pathway.  Thus, the cell line is an ideal tool for screening for antagonists of interactions between MC2 and its ligands.

     

    Additional Resource :  HTS021C052215 Datasheet

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    Contents: 2 vials of mycoplasma-free cells, 1 ml per vial.
    Storage: Vials are to be stored in liquid N2.
    Applications: Calcium Flux Assay
    Host Cell: Chem-1, an adherent cell line expressing the promiscuous G-protein, Gα15.
    Exongenous Gene Expression: Human MC2 cDNA (Accession Number: NM_000529) and promiscuous G protein are expressed in a bicistronic vector
    GMO: This product contains genetically modified organisms.
    Reference 1: 1. Gantz I and Fong TM (2003) The melanocortin system. Am. J. Physiol. Endocrinol. Metab. 284: E468-E474.
    Reference 2: 2. Clark A and Metherell L (2006) Mechanisms of Disease: the adrenocorticotropin receptor and disease. Nature 2(5):282-90. Review
    Reference 3: 3. Clark A et al. (1993) Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet 341: 461-462.
    Reference 4: 4. Imamine H et al. (2005) Possible relationship between elevated plasma ACTH and tall stature in familial glucocorticoid deficiency. Tohoku J Exp Med 205: 123-131.
    Reference 5: 5. Clark A et al. (2005) Inherited ACTH insensitivity illuminates the mechanisms of ACTH action. Trends Endocrinol Metab 16(10): 451-457.
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