Transcript cell signaling power point

Chapter 11: cell signals
Without cell signaling, no multicellular organisms
could exist.
Cells would use their genomes equivalently.
Cell signals allow cells to cooperate, signaling each
other about how gene expression (use of the
DNA) should be regulated:
which genes to transcribe,
which transcripts to translate,
how long proteins should last before destruction,
which proteins should be active.
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219 /220 human cell types contain identical genomes.
How is this possible?
Simplified summary:
Signal transduction mediated Gene expression.
Starts before conception.
Ends after death.
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For example, during embryonic development, a
subset of cells express genes coding for proteins
needed for muscle form and function.
Signal molecules from
Other cells in the embryo
(shown in red) control this
Switch in gene expression.
http://www.dmd.nl/images/myod_method_fig1.jpg
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Differentiation’s restriction of gene expression allows
cells to specialize. Different kinds of cells make
different proteins.
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Humans have about 220 types of specialized cells
that arise from the layers of the folded embryo, a
gastrula. The cells carry out different tasks.
Zygote –totipotent (all
types cells can be
formed from it).
1st 10 days: embryonic
stem cells (nearly
totipotent)
By the time the gastrula
forms within 10 days,
cells are pluripotent
and called adult stem
cells—committed to
one of a few fates.
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normal animal development:
zygote morula blastulagastruladifferentiated
(specialized cells)tissuesorgansorgan systems
organism
Tissues
Organs
Organ
systems
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The difference in whether a cell type chooses one developmental
pathway (e.g., brain versus muscle) can be as subtle as how many
copies of different transcripts are available. This is particularly true
during early development. Bicoid encodes a homeodomain protein
that is a transcription factor.
Frequent targets (effector proteins) of
early control genes are homeodomain
proteins like bicoid, determining
future responses of the cells.
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During development, cells become differentiated if the
effector (final step in the signal transduction cascade) for
the signal is a transcription factor in the nucleus.
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e.g., when signaled by other cells during development, some
cells of the mesoderm (middle layer of the gastrula) activate a
whole set of genes that result in cells becoming muscle cells.
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Complex body structures (like a head or a
whole body segment) develop in response to
developmental signals if the effector activates a
master control gene like a homeotic gene
• Homeotic genes code transcription factors that
recognize a particular set of nucleotides in other
genes, binding to them and activating their
transcription.
• Whole sets of genes needed to build a particular
body structure can be activated simultaneously by
the same signal molecule and its matching receptor
protein.
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Antenopedia, Noggin, and Trithorax Homeotic gene
mutations show how activation of a single master
control gene by a cell signal can have a dramatic
effect on development.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A2609
ncbi.nlm.nih.gov
http://neurophilosophy.wordpress.com/2006/08/09/the-role-ofhox-genes-in-development/
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Post-translational modifications allow membrane receptor
proteins to convey signals.
Via multi-protein signal transduction cascades that end
with an effector protein (does the signalled task).
Adding phosphate groups changes the
3D shape (tertiary structure) of
proteins in the signal pathway.
Kinases are protein enzymes that add
phosphate groups to another
protein.
This shape change may switch the
protein from inactive to active 3D
conformation.
Later, a phosphatase (phosphate
group removing enzyme) returns
each protein to its inactive shape.
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Normal development and normal day to day
cooperative activity of cells requires that signals
be sent in the right cells at the right times and at
the correct levels.
Diseases like cancer, diabetes, dwarfism occur
due to miscommunication of cells.
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What changes in gene expression cause cancer, a disease in
which cells cycle abnormally?
Effectors for growth factor
receptor mediated signal
pathways activate transcription
factors that make proteins
needed to stimulate cell division.
Cancer often arise due
to activating mutations
(gain of function)
of proteins in the growth factor
receptor mediated signal pathway.
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You must be able to sketch and
label the signalling molecules, plus
discuss the importance, of
• Tyrosine kinase receptor signal pathways
• G protein linked receptors that activate
PKCignal pathways
• G protein linked receptors that activate PLC
signal pathways
• Steroid receptor signal pathways
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Tyrosine kinase receptor pathways
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Tyrosine kinases activate downstream kinases, then
return to inactive states when dephosphorylated by
a phosphatase. They can be reused.
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G protein linked receptor proteins utilize non-protein
“second messengers” and fall into 2 main categories:
PLC stimulating and PKC stimulating
PLC stimulating:
ultimate response is to release Ca ions from
intracellular stores so that proteins activated
by Ca++ binding are activated) –example:
during muscle contraction, acetylcholine
receptors link to a G protein, then to PLC that
makes lipids (DAG, etc) that cause Ca release
from special ER called sarcoplasmic reticulum.
This allows muscle contraction.
http://www.youtube.com/watch?v=WRxsOMen
NQM
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G protein linked receptor proteins utilize nonprotein “second messengers” and fall into 2 main
categories: PLC stimulating (ultimate response is to
release Ca ions from intracellular stores so that
proteins activated by Ca++ binding are activated)
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PKC stimulating
Signal receptor G protein phosphorylated
G protein (active) activate adenyl cyclase
make second messenger cAMP activate
protein kinase A (PKA) activate effectors
http://www.youtube.com/watch?v=DGkh7SGac
gk
e.g. many neurotransmitters work this way
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