Akt signalling leads to stem cell activation and promotes tumour development in epidermis.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48522 | GEO | 2014/01/26
SECONDARY ACCESSION(S): PRJNA210424
REPOSITORIES: GEO
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Project description:Cursons2015 - Regulation of ERK-MAPK
signaling in human epidermis
Model comparing the abundance of
phosphorylated MAPK signalling proteins and calcium signalling in
the epidermis.
This model is described in the article:
Regulation of ERK-MAPK
signaling in human epidermis.
Cursons J, Gao J, Hurley DG, Print
CG, Dunbar PR, Jacobs MD, Crampin EJ.
BMC Syst Biol 2015; 9: 41
Abstract:
The skin is largely comprised of keratinocytes within the
interfollicular epidermis. Over approximately two weeks these
cells differentiate and traverse the thickness of the skin. The
stage of differentiation is therefore reflected in the
positions of cells within the tissue, providing a convenient
axis along which to study the signaling events that occur in
situ during keratinocyte terminal differentiation, over this
extended two-week timescale. The canonical ERK-MAPK signaling
cascade (Raf-1, MEK-1/2 and ERK-1/2) has been implicated in
controlling diverse cellular behaviors, including proliferation
and differentiation. While the molecular interactions involved
in signal transduction through this cascade have been well
characterized in cell culture experiments, our understanding of
how this sequence of events unfolds to determine cell fate
within a homeostatic tissue environment has not been fully
characterized.We measured the abundance of total and
phosphorylated ERK-MAPK signaling proteins within
interfollicular keratinocytes in transverse cross-sections of
human epidermis using immunofluorescence microscopy. To
investigate these data we developed a mathematical model of the
signaling cascade using a normalized-Hill differential equation
formalism.These data show coordinated variation in the
abundance of phosphorylated ERK-MAPK components across the
epidermis. Statistical analysis of these data shows that
associations between phosphorylated ERK-MAPK components which
correspond to canonical molecular interactions are dependent
upon spatial position within the epidermis. The model
demonstrates that the spatial profile of activation for
ERK-MAPK signaling components across the epidermis may be
maintained in a cell-autonomous fashion by an underlying
spatial gradient in calcium signaling.Our data demonstrate an
extended phospho-protein profile of ERK-MAPK signaling cascade
components across the epidermis in situ, and statistical
associations in these data indicate canonical ERK-MAPK
interactions underlie this spatial profile of ERK-MAPK
activation. Using mathematical modelling we have demonstrated
that spatially varying calcium signaling components across the
epidermis may be sufficient to maintain the spatial profile of
ERK-MAPK signaling cascade components in a cell-autonomous
manner. These findings may have significant implications for
the wide range of cancer drugs which therapeutically target
ERK-MAPK signaling components.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000659.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
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