11-Cell Communications_1x
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Transcript 11-Cell Communications_1x
Cell Communications
https://www.yout
ube.com/watch?v
=W-1UfjdSbgo
Overview
Signal reception
and the initiation of
transduction
Transduction
pathways
Cellular responses
to signals
http://www.bio.miami.edu/dywang/150lec-10.html
http://www.youtube.com/watch?NR=1&v=tMMrTRnFdI4
Overview of Cell Signaling
Proximity is a factor
Local regulators are nearby
cells
1) paracrine signaling
2) synaptic signaling
Hormones are long
distance signals
Reception, transduction
and response
https://www.youtube.com/watch?v=tkguTfVqvsM
http://www.hhmi.org/bulletin/february-2012/prialt-paralyzes-fish
http://www.hhmi.org/bulletin/february-2012/prialt-blocks-painsignaling-mice
Stages of cell signaling
Glycogen depolymerization by epinephrine
3 steps:
•Reception: target cell detection
•Transduction: single-step or series of changes
•Response: triggering of a specific cellular response
Signal reception and the
Initiation of Transduction
Chemical signals (ligands)
bind to receptor
proteinchanges shape
Most receptors are plasmamembrane proteins
1)Tyrosine-kinase receptors
2) G-protein-linked
receptors
3)Ion-channel receptors
https://www.youtube.com/watch?v=NXOXZkaSVI
http://www.youtube.com/watch?v=V_0EcUr_txk&feature=related
Second Messengers
http://www.youtube.com/watch?v=K7WSMybZeA8
In response to a signal relayed by a signal
transduction pathway, the cytosolic calcium
level may rise, usually by a mechanism that
releases Ca2 from the cell’s ER. The pathways
leading to calcium release involve still other
second messengers, inositol trisphosphate
(IP3) and diacylglycerol (DAG).
These two messengers are produced by cleavage
of a certain kind of phospholipid in the plasma
membrane.
https://www.youtube.com/watch?v
=2bbBrpgeheY
Signal Transduction Pathways
Relay signals from
receptors to responses
Protein
phosphorylation major
mechanism
Roles of cyclic AMP,
calcium ions and
inositol triphosphate
http://www.youtube.com/watch?v=iGb93jCKVXs&feature=related
Cellular Responses to Signals
Signal amplification
Signal specificity
Here is a simplified pathway
Here is a more complete view of a signal transduction
pathway involving tumor necrosis factor .
cholera
The cholera toxin is an enzyme that chemically modifies a
G protein involved in regulating salt and water secretion.
Because the modified G protein is unable to hydrolyze
GTP to GDP, it remains stuck in its active form,
continuously stimulating adenylyl cyclase to make cAMP.
The resulting high concentration of cAMP causes the
intestinal cells to secrete large amounts of salts into the
intestines, with water following by osmosis through the
CFTR protein
“Woe to the child which when kissed on the forehead
tastes salty. He is bewitched and soon will die” - old proverb
apoptosis
http://www.youtube.com/watch?v=9KTDzZisZ0
http://www.youtube.com/watch?v=v1PWcX
66ucI&feature=related
The molecular mechanisms underlying
apoptosis were worked out in detail by
researchers studying embryonic development
of a small soil worm, a nematode called
Caenorhabditis elegans.
The timely suicide of cells occurs exactly
131 times during normal development of C.
elegans, at precisely the same points in the
cell lineage of each worm.
The main proteases of apoptosis are called
caspases
In humans and
other mammals,
several different
pathways,
involving about 15
different caspases,
can carry out
apoptosis. The
pathway that is
used depends on
the type of cell and
on the particular
signal that initiates
apoptosis.
http://www.youtube.com/watch?v=jo8gx61BR-Y
P53- tumor suppressor
http://www.youtube.com/watch?v=RxwYoevYZYs
p53 (also known as protein 53 or tumor protein
53), is a tumor suppressor protein that in humans is
encoded by the TP53 gene. p53 is crucial in
multicellular organisms, where it regulates the cell
cycle and, thus, functions as a tumor suppressor that
is involved in preventing cancer. As such, p53 has
been described as "the guardian of the genome"
because of its role in conserving stability by
preventing genome mutation.
http://www.youtube.com/watch?v=iGQdwSAAz9I
Proto-oncogenes and Oncogenes
Oncogenes arise
when protooncogenes mutate
or are moved (or
amplified) to a
part of the
genome where
their expression is
greatly
heightened.
The BCR-ABL fusion gene causes chronic myelogenous leukemia. The
experimental drug STI 571 competes with ATP to block the action of the
fusion protein, thus stopping the cancer.
http://www.emp
iregenomics.co
m/shop/BCRABL1-FISHProbe.html
http://www.youtube.c
om/watch?v=dpgxB9
xXIHs
Scientists have divided oncogenes
into the 5 different classes
Growth factors
These genes produce factors that stimulate cells to grow.
Growth factor receptors
These genes are normally turned "on" or "off" by growth factors.
Certain mutations in the genes that produce these cause them to
always be "on." In other cases, the genes are amplified.
As a result, the cells become overly sensitive to growth-promoting
signals.
Signal transducers
These are the intermediate pathways between the growth factor
receptor and the cell nucleus where the signal is received.
Transcription factors
These molecules act on the DNA and control which genes are active
in producing RNA and protein
Programmed cell death regulators
The abnormal production of these molecules prevent a cell from
committing suicide when it becomes abnormal
HER2 (human epidermal growth factor receptor 2) is a
protein that plays an important role in how cells grow,
multiply, and survive. HER2 is produced by the HER2/neu
gene. Normal cells contain two copies of the HER2 gene
and make amounts of HER2 to allow normal cell growth and
division. Some cancer cells, however, contain many more
copies of the HER2 gene and in turn produce too much
HER2 protein. This "overexpression" of HER2 receptors
results in a cancer that is "HER2+."
Trastuzumab (Herceptin) is a drug called a monoclonal
antibody that has been approved for use by the FDA. It
works by preventing the HER2/neu protein from promoting
excessive growth of cancer cells.
Human Epidermal growth factor Receptor
2
Monoclonal antibodies
are antibodies that are identical because they were
produced by one type of immune cell, all clones of
a single parent cell.
Given any substance, it is possible to create
monoclonal antibodies that specifically bind to that
substance
The tissue culture cells made from fusion of a
plasma cell, which is the antibody producer and the
myeloma cell, which provides longevity and ability
to make large amounts of antibody
http://www.youtube.com/watch?v=4NH2ldNPeRo
http://www.youtube.com/watch?v=lcHy8THENXo