1289 39 3228 7 4619 document 3228 Decl_IS_Kendrick_PhD_11.pdf application/pdf e4d48f54e0c6784409311ce0b9c51021 MD5 80115 2011-07-19 16:32:44 http://etheses.bham.ac.uk//id/eprint/1289/2/Decl_IS_Kendrick_PhD_11.pdf 1289 2 1 application/pdf application/pdf en validuser

Decl_IS_Kendrick_PhD_11.pdf

http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6191 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6191 http://eprints.org/relation/hasIndexCodesVersion http://etheses.bham.ac.uk/id/document/6191 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6207 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6207 http://eprints.org/relation/hassmallThumbnailVersion http://etheses.bham.ac.uk/id/document/6207 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6208 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6208 http://eprints.org/relation/haspreviewThumbnailVersion http://etheses.bham.ac.uk/id/document/6208 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6217 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6217 http://eprints.org/relation/hasIndexCodesVersion http://etheses.bham.ac.uk/id/document/6217 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/13990 http://eprints.org/relation/haspreviewThumbnailVersion http://etheses.bham.ac.uk/id/document/13990 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/13990 3229 6 4620 document 3229 Kendrick_11_PhD.pdf application/pdf 389bf8f96be2cc53c14b40f976487e38 MD5 7287878 2011-07-19 16:32:44 http://etheses.bham.ac.uk//id/eprint/1289/1/Kendrick_11_PhD.pdf 1289 1 3 application/pdf application/pdf en public

Kendrick_11_PhD.pdf

http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6189 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6189 http://eprints.org/relation/hassmallThumbnailVersion http://etheses.bham.ac.uk/id/document/6189 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6190 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6190 http://eprints.org/relation/haspreviewThumbnailVersion http://etheses.bham.ac.uk/id/document/6190 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/6192 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/6192 http://eprints.org/relation/hasIndexCodesVersion http://etheses.bham.ac.uk/id/document/6192 6189 2 8312 document 6189 small.png image/png 028de9e95d48db8c8ffb511831940eba MD5 3969 2011-07-19 19:04:08 http://etheses.bham.ac.uk//id/eprint/1289/3/small.png 1289 3 3 image/png thumbnail_small Thumbnail Documents conversion from application/pdf to thumbnail_small en public

small.png

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/issmallThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3229 6190 2 8313 document 6190 preview.jpg image/jpeg 1b43bb3548020db3c8ad0af013c1fa8f MD5 11383 2011-07-19 19:04:09 http://etheses.bham.ac.uk//id/eprint/1289/4/preview.jpg 1289 4 4 image/jpeg image/jpeg Thumbnail Documents conversion from application/pdf to thumbnail_preview en public

preview.jpg

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3229 6207 2 8333 document 6207 small.png image/png 871f34ebcd5d54fb5e52ea180f0d5874 MD5 7515 2011-07-19 19:05:20 http://etheses.bham.ac.uk//id/eprint/1289/7/small.png 1289 7 7 image/png thumbnail_small Thumbnail Documents conversion from application/pdf to thumbnail_small en validuser

small.png

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/issmallThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3228 6192 2 8316 document 6192 indexcodes.txt text/plain 43ad086fbe0a697653f1f139ecb291d0 MD5 46424 2011-07-19 19:04:14 http://etheses.bham.ac.uk//id/eprint/1289/6/indexcodes.txt 1289 6 6 text/plain indexcodes Generate index codes conversion from application/pdf to indexcodes en public

indexcodes.txt

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3229 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/3229 6208 2 8334 document 6208 preview.jpg image/jpeg 4202fcd1685732c04792ce9852df5e88 MD5 28683 2011-07-19 19:05:20 http://etheses.bham.ac.uk//id/eprint/1289/8/preview.jpg 1289 8 8 image/jpeg image/jpeg Thumbnail Documents conversion from application/pdf to thumbnail_preview en validuser

preview.jpg

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3228 6217 2 8344 document 6217 indexcodes.txt text/plain fc4e0483fdf7ed526a94c076137eb9d6 MD5 2990 2011-07-19 19:06:13 http://etheses.bham.ac.uk//id/eprint/1289/9/indexcodes.txt 1289 9 9 text/plain indexcodes Generate index codes conversion from application/pdf to indexcodes en validuser

indexcodes.txt

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/3228 13990 2 21257 document 13990 preview.png image/png d9bb3e86336ab0a0a5cdd5b31df64e2a MD5 30494 2011-07-21 10:54:23 http://etheses.bham.ac.uk//id/eprint/1289/10/preview.png 1289 10 10 image/png image/png en validuser

preview.png

http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3228 http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3228 archive 4031 disk0/00/00/12/89 2011-01-19 10:17:14 2019-01-23 09:53:51 2011-07-19 16:32:44 thesis show 0 Kendrick Rachel Wheatley Mark University of Birmingham unpub Q1 QH426 QH QH301 10col_life The peptide hormone, ghrelin, exerts its physiological effects through a G-protein-coupled receptor called the ghrelin-R. The ghrelin-R displays a high degree of constitutive activity, signalling through the inositol phosphate pathway in the absence of bound agonist. TMs III and VI have been reported to be central to the activation of Family A GPCRs, with interactions between the two helices stabilising the ground state. During activation conformational rearrangements result in these interactions being broken, with new contacts forming and stabilising the active state. Investigation of the ghrelin-R constitutive activity gives an insight into the mechanisms involved in receptor activation. In this study the role of specific individual residues in the ghrelin-R has been investigated and the effect of disrupting or introducing intramolecular interactions was addressed. Site-directed mutagenesis and functional assays revealed that ghrelin-R constitutive activity can be increased and decreased with mutation of residues within the TM domains, specifically TMs III, VI and VII. The extracellular loops have been found to be involved in ligand binding and activation in a number of Family A GPCRs. The residues within ECL2 of the ghrelin-R were systematically mutated to alanine to determine their role. In particular, one residue, Asn196, was identified as being critical in ghrelin-R function and may be forming stabilising interactions which maintain ghrelin-R constitutive activity. The data presented in this thesis provide an insight into the structure and function of the ghrelin-R and the underlying molecular mechanisms of ghrelin-R constitutive activity. 2011-07 2010-09 graduation eng This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Ferring Research Institute, Inc. public 312 University of Birmingham School of Biosciences d_ph bbsrc 2011-07 graduation