KEY - CH 11 RG (powerpoint)

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1) What is a signal transduction
pathway?
● the process by which a
signal on a cell’s
surface is converted
into a specific cellular
response (a series of
steps)
2) How do yeast cells communicate
while mating?
● chemical signaling
● 2 mating types: a and α (alpha)
-type “a” cells secrete “a” factor
-type “α” cells secrete “α” factor
● the factors bind to receptors on the other;
the 2 mating factors cause the cells to grow
toward each other and fuse
3) How do intercellular connections
function in cell to cell
communication?
● both plant and animal cells have cell
junctions (gap junctions in animal cells;
plasmodesmata in plant cells) that, where
present, directly connect the cytoplasms of
adjacent cells
● signaling substances dissolved in the
cytoplasm can freely pass between adjacent
cells
4) Explain the two types of local
signaling:
A) Paracrine signaling
● a secreting cell acts on nearby target cells
by releasing molecules of a local regulator
(i.e. growth factor) into the extracellular fluid
4) Explain the two types of local
signaling:
B) Synaptic signaling
● a nerve cell releases
neurotransmitter molecules
into a synapse, the narrow
space between the
transmitting cell & the
target cell
5) How are long distance signals
sent?
● Long distance signals are sent by chemicals
called HORMONES.
● specialized endocrine cells secrete
hormones into body fluids,often the blood.
● hormones may reach virtually all body cells,
but will only attach to target cells with the
specific receptor molecule
6) Explain Sutherland’s investigations
with epinephrine and the inferences
that were derived from this work.
● discovered that epinephrine stimulates glycogen
breakdown by activating a cytosolic enzyme,
glycogen phosphorylase.
● this only worked when epinephrine was applied to
intact cells
● INFERENCE: epinephrine does not act on the
enzyme directly; and the cell membrane is
somehow involved in transmitting the signal
7) Define the three stages of cell
communication:
A) Reception:
● the target cell’s detection of a
signal coming from outside the
cell
● a chemical signal is detected
when it binds to a cellular protein
(usually a membrane protein)
7) Define the three stages of cell
communication:
B) Transduction:
● the binding of the signal
molecule changes the
receptor protein in
some way…
● the signal is converted
to a form that can bring
about a specific cellular
response
7) Define the three stages of cell
communication:
C) Response
● the transduced signal finally
triggers a specific cellular
response
8) What is a ligand?
● a small molecule that specifically binds to a
larger one
● a signal molecule behaves as a ligand
9) What is special about intracellular
receptors – hint think of the structure
of the cell membrane and how this
relates?
● intracellular receptors are typically proteins
dissolved in the cytosol or nucleus of a
target cell
● may become activated with the binding of
the signal molecule
● the activated form may then respond or
cause a change (i.e. enter the nucleus and
turn on specific genes)
10) Label
this diagram
of a steroid
interacting
with an
intracellular
receptor.
(Fig. 11.9)
11) Where would you expect most water
soluble messengers to bind and why?
● would most likely bind to receptors on the
outside surface of the plasma membrane;
● they are water-soluble & probably too large
to pass through the cell membrane
12) What is a G-protein-linked
receptor? (see fig. 11.7)
● a plasma membrane receptor that works
with the help of a G-protein
● the G-protein is attached to the cytoplasmic
side of the membrane and acts as a switch
that is on (GTP) or off (GDP)
13) (see fig. 11.7, p. 211 captions):
(overview): A G-protein-coupled receptor is a cellsurface transmembrane receptor that works
with the help of a G protein, a protein that binds
the energy-rich molecule GTP .
(1) When GDP is bound to the G protein, the G
protein is inactive. The receptor and G protein
work together with another protein, usually an
enzyme
.
13) (see fig. 11.7, p. 211 captions):
(2) When the appropriate signaling molecule binds to
the extracellular side of the receptor, the receptor
is activated and
changes shape
. Its
cytoplasmic side then binds an inactive G protein,
causing a GTP to displace GDP . This
activates the G protein.
13) (see fig. 11.7, p. 211 captions):
(3) The activated G protein leaves (dissociates from)
the receptor, diffuses along the membrane, and
then binds to an
enzyme , altering the
enzyme’s
shape
&
activity
. Once
activated, the enzyme can trigger the next step,
leading to a
cellular response
.
13) (see fig. 11.7, p. 211 captions):
(4) The changes in the enzyme and G protein are
only temporary because the G protein also
functions as a GTPase
enzyme – in other
words, it then hydrolyzes its bound GTP to GDP.
Now inactive again, the G protein
leaves
the enzyme, which returns to its original state. The
GTPase function of the G protein allows the
pathway to
shut down
rapidly when the
signaling molecule
is no longer present.
14) What is a KINASE (i.e. a protein
kinase)?
● an enzyme that catalyzes the transfer of a
phosphate group from ATP to another
molecule
15) (see fig. 11.7, p. 212 captions):
(overview): Receptor tyrosine kinases belong to a major class
of plasma membrane receptors characterized by having
enzymatic activity. The part of the receptor protein
extending into the cytoplasm functions as a tyrosine kinase,
an enzyme that catalyzes the transfer of
a phosphate
group
from ATP to the amino acid
tyrosine
on a substrate protein. One receptor tyrosine kinase
complex may activate ten or more different transduction
pathways and cellular responses. The ability of a single
ligand-binding event to trigger so many pathways is a key
difference between
receptor-tyrosine kinases
and
G protein-coupled receptors
.
15) (see fig. 11.7, p. 212 captions):
(1) Before the signaling molecule binds, the
receptors exist as
individual units
referred to as monomers. Each monomer
has an extracellular
ligand-binding
site, an α helix spanning the membrane,
and an intracellular tail containing multiple
tyrosines .
15) (see fig. 11.7, p. 212 captions):
(2) The binding of a signaling molecule
(such as growth factor) causes 2 receptor
monomers to
associate closely with
each other , forming a complex known as
a dimer (dimerization).
15) (see fig. 11.7, p. 212 captions):
(3) Dimerization activates the tyrosine
kinase region of each monomer; each
tyrosine kinase adds a phosphate from
an ATP molecule to a tyrosine on the tail of
the other monomer.
15) (see fig. 11.7, p. 212 captions):
(4) Now that the receptor is fully activated
, it is recognized by specific relay proteins
inside the cell. Each such protein binds to a
specific phosphorylated tyrosine, undergoing
a resulting structural change that activates
the bound protein. Each activated protein
triggers a transduction pathway , leading
to a cellular response .
16) (see fig. 11.7, p. 213 captions):
(overview): What triggers a ligand-gated ion
channel to open/close? when a signaling
molecule binds as a ligand to the
receptor protein
What then passes through the channel once it
is open?
Specific ions, such as Na+ or
Ca2+, pass through the channel receptor
16) (see fig. 11.7, p. 213 captions):
**study and read the captions for parts 1-3 of this
diagram!
(conclusion): How do nerve cells make use of
ligand-gated ion channels?
neurotransmitter molecules released at a
synapse between 2 nerve cells bind as
ligands to ion channels on the receiving
cell, causing the channels to open; as ions
flow in/out, an electrical signal is generated
and passed down the receiving cell…a
nerve impulse!
16) (see fig. 11.7, p. 213 captions):
How is a voltage-gated ion channel different?
these channels are controlled (opened
/ closed) by electrical signals (not ligands
/ chemical signals) .
16) DIAGRAM: Ligand-gated ion channel
17) (see fig. 11.10, p. 215 captions):
(overview): Summarize what occurs in a
phosphorylation cascade: a series of
different molecules in a pathway are
phosphorylated in turn, each molecule
adding a phosphate group to the next
one in line .
(1) A relay molecule
activates protein
kinase 1
.
17) (see fig. 11.10, p. 215 captions):
(2) Active protein kinase 1 transfers
a phosphate from ATP to an
inactive molecule of protein kinase 2,
thus activating this 2nd kianse.
(3) Active protein kinase 2 then catalyzes
the phosphorylation (& activation )
of protein kinase 3.
17) (see fig. 11.10, p. 215 captions):
(4) Finally, active protein kinase 3
phosphorylates a protein that brings about
the cell’s response to the signal.
(5) Enzymes called protein phosphatases
(PP) catalyze the
removal of the
phosphate groups from the proteins,
making them
inactive
&
available
for reuse.
18) What are protein phosphatases
and why are they so important?
● enzymes that remove
phosphate groups from
proteins
● they help to rapidly turn off
a signal-transduction
pathway then the initial
signal is no longer present
19) What are second messengers and
what are two characteristics of a
second messenger?
● molecules that are
involved in the signaltransduction pathway
(other than the first
messenger)
● small, non-protein, watersoluble
20) What did Sutherland find in his
experiments with regard to cyclic
AMP and why is this important?
● the binding of epinephrine caused an
elevation of the cytosolic concentration of
cyclic AMP.
● an enzyme in the plasma membrane,
adenylyl cyclase, converts ATP to cAMP,
which then broadcasts the signal to the cell
● this mechanism is used in many signaltransduction pathways
21) What is adenylyl cyclase?
● an enzyme in the plasma membrane that
converts ATP to cAMP in response to an
extracellular signal
22)
Complete
the diagram
below of
cAMP as
second
messenger:
23) How does cholera connect with
the concepts of cell to cell
communication?
● the bacteria that cause cholera colonize the lining of the
small intestine and produce a toxin, which is an enzyme
that chemically modifies a G-protein involved in regulating
salt and water secretion
● the modified G-protein cannot hydrolyze GTP to GDP and
remains in its active form, continuously stimulating the
production of cAMP…
● this continuously stimulates the intestinal cells to secrete
large amounts of water and salts into the intestines…
● an infected person quickly develops profuse diarrhea and
could die from loss of water and salts
24) How does the drug “Viagra” work? Why was
it originally prescribed for chest pain?
● in one cell signaling pathway, cyclic GMP
(cGMP) acts as a signaling molecule whose
effects include relaxation of smooth muscle
cells in artery walls; VIAGRA is a drug /
compound that inhibits they hydrolysis of
cGMP back to GMP, thus prolonging the
signal (keeps blood vessels open)
● originally prescribed for chest pains because
it increased blood flow to the heart muscle
25) How and why are the calcium concentrations
kept different and separate comparing the
endoplasmic reticulum, mitochondria and
cytoplasm?
● calcium concentrations are kept different
and separate from the active transport of
Ca2+ ions by various protein pumps
● this is done so that Ca2+ ions can be used as
second messengers
26) Label the diagram below showing calcium
and IP3 in a cell.
27) Label the
diagram below
showing nuclear
responses to a
signal.
28) How is signal amplification
accomplished in the cell?
● at each step in the pathway, the # of
activated products is much greater than in
the preceding step (the proteins/enzymes at
each step stay in “active” form long enough
to process many molecules of substrate
before becoming inactive again)
29) How is specificity accomplished in
cell signaling?
● the response of a
particular cell to a
signal depends on its
particular collection of:
signal receptor
proteins, relay
proteins, and proteins
needed to carry out
the response.
30) What is a scaffolding protein and
why is it important?
● a large relay protein to which several other
relay proteins are simultaneously attached
● this facilitates signal-transduction pathways
because it gathers together all of the
proteins involved in the pathway; it enhances
speed and accuracy of signal transfer
31) Label the diagram of a scaffolding protein
shown here. (fig. 11.19)
32) How is termination of a signal accomplished
and why is it so important that termination be
accomplished?
● when a signal molecule leaves the receptor,
the receptor reverts to its inactive form & the
relay proteins return to their inactive forms
 GTPase hydrolyzes GTP to GDP
 cAMP is converted back to AMP
 phosphatases inactivate kinases, etc.
● this is important so that a cell may continue
to be receptive to a particular signal
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