Amino Acid Residues Implicated in the Interaction of Melanocortin Ligands and Their Receptors: A Study of MC2R Selectivity

<p>Melanocortin receptor ligand selectivity has been a question not easily answered. The inability to functionally express melanocortin 2 receptor (MC2R) has inhibited the study of why MC2R is only stimulated by ACTH, a melanocortin hormone. With the recent discovery of the MC2R accessory protein (MRAP), creating a heterologous system is now feasible. Using a general cell line like CHO-K1 cells, which do not express endogenous MCRs, we were able to create a heterologous expression system and test the selectivity of MC2R using analog variants of ACTH(1-24). Our results indicate an amino acid requirement in the C-terminal portion of ACTH(1-24) for activation, which supports the 2-step method of activation hypothesized for MC2R. This site, the tetra basic cleavage site, when altered does not stimulate cAMP production and does not compete with ACTH(1-24) for binding. We also demonstrate the potential for a non-mammalian MC2R system in cloning full length <em>Silurana tropicalis</em> MC2R and completed localization studies with this system with MRAP using CHO-K1 cells.</p>

Name thesis:degree_name

M.S.

Level thesis:degree_level

Masters Thesis

Year dc:date.available

2009

Author dc:creator

• Veo, Kristopher D.

Contributors dc:contributor

• Robert M. Dores, Ph.D.
• Cynthia V. Fukami
• Joseph Angleson
• Scott Barbee

• ACTH
• Adrenocorticotropic hormone
• Activation
• CHO-K1
• MC2R
• Melanocortin 2 receptor
• Melanocortin
• Silurana Tropicalis
• Biology
• Molecular Biology

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

en

Repository record dc:identifier

https://digitalcommons.du.edu/etd/945

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-1944