Linear domain interactome and biological function of anterior gradient 2
dc.contributor.advisor
Hupp, Ted
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dc.contributor.advisor
Hastie, Nicholas
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dc.contributor.advisor
Satsangi, Jack
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dc.contributor.advisor
Hohenstein, Peter
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dc.contributor.author
Lawrence, Melanie Laura Alexandra
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dc.contributor.sponsor
Medical Research Council (MRC)
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dc.date.accessioned
2015-10-09T14:20:53Z
dc.date.available
2015-10-09T14:20:53Z
dc.date.issued
2013-11-29
dc.description.abstract
The Anterior Gradient 2 (AGR2) protein has been implicated in a variety
of biological systems linked to cancer and metastasis, tamoxifen-induced drug
resistance, pro-inflammatory diseases like IBD and asthma, and limb regeneration.
The molecular mechanisms by which AGR2 mediates these various
phenotypes in disease progression in both cancer and IBD are poorly understood,
as is the biological function(s) of AGR2 under non-disease conditions.
Here, we use a combination of biochemical techniques, organ culture, cell biology
and mouse genetics to investigate the biological significance of AGR2
both in cell lines and in vivo. We present data based on phage-peptide inter-actomics
screens suggesting a role for AGR2 in mediating the maturation and
trafficking of a class of membrane and secretory proteins, and investigate a putative
interaction between AGR2 and one member of this class of proteins. We
also describe the construction of a universal vector for use in making a variety
of transgenic animals, and then present data showing its use as a promoter
reporter, and attempt to investigate the temporal and spatial expression of
AGR2 in the developing and adult mouse. Further, we present data describing
the localisation pattern of AGR2 in the developing murine kidney using
a combination of organ culture and antibody staining, and suggest a role for
AGR2 in the developing kidney based on this data that is in agreement with
a chaperone function for membrane and secretory proteins. Together, these
data suggest that AGR2 has an intrinsic consensus docking site for a subset
of its client proteins, that AGR2 plays a role in protein maturation in ciliated
cell types, and provides a novel biological model to dissect the role of AGR2
in ER-trafficking.
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dc.identifier.uri
http://hdl.handle.net/1842/10638
dc.language.iso
en
dc.publisher
The University of Edinburgh
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dc.relation.hasversion
Karamjit Singh Dolt, Melanie L. Lawrence, Eve Miller-Hodges, Anna Thornburn, Paul Devenney and Peter Hohenstein (2013) A Universal Vector for High-Efficiency Multi-Fragment Recombineering of BACs and Knock-In Constructs. PLoS ONE 8(4): e62054. doi:10.1371/journal.pone.0062054
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dc.subject
AGR2
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dc.subject
Anterior Gradient 2
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dc.subject
linear peptide
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dc.subject
Meckelin
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dc.subject
MKS3
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dc.subject
BAC transgenics
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dc.title
Linear domain interactome and biological function of anterior gradient 2
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dc.type
Thesis or Dissertation
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dc.type.qualificationlevel
Doctoral
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dc.type.qualificationname
PhD Doctor of Philosophy
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