When epinephrine is mixed with glycogen phosphorylase and glycogen in a test tube, is glucose 1-phosphate generated? Why or why not?
Glucose 1-phosphate is not generated, because the activation of the enzyme requires an intact cell, with an intact receptor in the membrane and an intact signal transduction pathway. The enzyme cannot be activated directly by interaction with the signalin
In liver cells, glycogen phosphorylase acts in which of the three stages of the signaling pathway associated with an epinephrine initiated signal?
Glycogen phospohrylase acts in the third stage, the response to epinephrine signaling
Nerve growth factor is a water-soluble signaling molecule. Would you expect the receptor for NGF to be intracellular or in the plasma membrane? Why?
I would expect it to be in the plasma membrane because it is polar (hydrophilic) and would not be able to pass through the membrane
What would the effect be if a cell made defective receptor tyrosine kinase proteins that were unable to dimerize?
The cell with the faulty receptor would not be able to respond appropriately to the signaling molecule when it was present. This would likely have dire consequences for the cell, since regulation of the cell's activities by this receptor would not occur a
How is ligand binding similar to the process of allosteric regulation of enzymes?
Binding of a ligand to a receptor changes the shape of the receptor, altering the ability of the receptor to transmit a signal. Binding of an allosteric regulator to an enzyme changes the shape of the enzyme, either promoting or inhibiting enzyme activity
When a signal transduction pathway involves a phosphorylation cascade, how does the cell's response get turned off?
Protein phosphatases reverse the effects of the kinases
What is the actual "signal" that is being transduced in any signal transduction pathway? In what ways is this information being passed from the exterior to the interior of the cell?
The signal that is being transduced is the information that a signaling molecule is bound to the cell-surface receptor. Information is transduced by way of sequential protein-protein interactions that change protein shapes, causing them to function in a w
Review the discussion of protein phosphatases on page 216. Some human diseases are associated with malfunctioning protein phosphatases. How would such proteins affect signaling pathways?
A malfunctioning protein phosphatase would not be able to dephosphorylate a particular receptor or relay protein. As a result, the signaling pathway, once activated, would not be able to be terminated.
What types of protein defects could result in apoptosis occurring when it should not? What types could result in apoptosis not occurring when it should?
-If a receptor protein for a death-signaling molecule were defective such that it was activated even in the absence of the death signal, this would lead to apoptosis when it wouldn't normally occur.
-Similar defects in any of the proteins in the signaling
Phosphorylation cascades involving a series of protein kinases are useful for cellular signal transduction because
a. They are species specific
b. They always lead to the same cellular response
c. They amplify the original signal manifold
d. They counter
C.
Binding of a signaling molecule to which type of receptor leads directly to a change in the distribution of ions on opposite sides of the membrane?
a. Receptor tyrosine kinase
b. G protein coupled receptor
c. Phosphorlayed receptor tyrosine kinase dimer
d
D
The activation of receptor tyrosine kinases is characterized by
a. Dimerization and phosphorylation
b. Dimerization and IP3 binding
c. A phosphorylation cascade
d. GTP hydrolysis
e. Channel protein shape change
A
Lipid-soluble signaling molecules, such as testosterone, cross the membranes of all cells but affect only target cells because
a .Only target cells retain the appropriate DNA segments
b. Intracellular receptor are present only in target cells
c. Most cell
B
Consider this pathway: epinephrine --> G protein-coupled receptor ---> G protein --->adenylyl cylase--> cAMP
Identify the second messenger
a. cAMP
b. G protein
c. GTP
d. Adenylyl cyclase
e. G protein-coupled receptor
A
Apoptosis involves all but which of the following
a. Fragmentation of the DNA
b. Cell-signaling pathways
c. Activation of cellular enzymes
d. Lysis of the cell
e. Digestion of cellular contents by scavenger cells
D
Which observation suggested to Sutherland the involvement of a second messenger in epinephrine's effect on liver cells?
a. Enzymatic activity was proportional to the amount of calcium added to a cell-free extract
b. Receptor studies indicated that epineph
C
Protein phosphorylation is commonly involved with all of the following except
a. Regulation of transcription by extracellular signaling molecules
b. Enzyme activation
c. Activation of G protein-coupled receptors
d. Activation of receptor tyrosine kinases
C
Epinephrine initiates a signal transduction pathway that involves the production of cyclic AMP and leads to the breakdown of glycogen to glucose, a major energy source for cells. But glycogen breakdown is actually only part of the fight-or-flight response
-Caffeine blocks the activity of cAMP phosphodiesterase, making it inactive, shutting off the cycle. An individual experiences alertness and sleeplessness because there is a continuous production of cAMP.
Why is cell communication important?
-sex, mating of cells
-allows cells to talk to each other, coordinating activities
-many biological processes require cells to communicate
-in order for multi-cellular organisms to grow and develop, cells must communicate
Local signaling
-cell junctions
-cell to cell recognition and signaling
Cell Junctions
-cell junctions: both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes
Cell to cell recognition and signaling
direct contact: two cells in an animal may communicate by interaction between molecules protruding from their surfaces
By secretion of chemical messenger molecules:
-paracrine signaling: a secreting cell acts on nearby target cells by discharging molecule
Long distance signaling
-hormones
-endocrine signaling: specialized cells release hormone molecules which travel via circulatory system to other parts of the body, where they reach target cells that can respond to the hormones
-Transmission of a signal through
the nervous system
Give an example of a tissue that uses gap junctions for communications
...
Difference between local and long distance communication
local: use of local regulators
long distance: use of hormones
Hormone
one of many types of secreted chemicals that are formed in specialized cells, travel in body fluids, an act on specific target cells in other parts of the body, changing the target cell's functioning
-important in long-distance signaling
Example of a protein acting as a hormone
-insluin: regulates sugar levels in blood is a protein with thousands of atoms
Do all cells contain receptors for all signals? Do you think that all cells in a human have receptors for testosterone, or is that only some cells that have that receptor?
No, the ability of a cell to respond is determined by whether it has a specific receptor molecule that can bind to the signaling molecule
Discuss specificity in cellular communication
-in stage 1, reception, a signaling molecule binds to a receptor protein causing it to change shape.
-the signaling molecule is complementary in shape to a SPECIFIC site on the receptor and attaches there
Ligand
term for a molecule that specifically binds to another molecule, often a larger one
Receptor
Most are plasma membrane proteins with ligands that are
water soluble and too large to pass through the plasma
membrane
? Many are found in cytosol or nucleus [ligands must be
able to pass through the plasma (and nuclear) membrane
(i.e., must be hydrophob
Receptors in the plasma membrane
CANNOT PASS THROUGH PLASMA MEMBRANE; WATER SOLUBLE
-G protein-coupled receptors
-receptor tyrosine kinases
-ion channel receptors
Intracellular receptors
-found in either cytoplasm or nucleus of target cells
Nitric oxide?small enough to pass
through the plasma membrane; a local
regulator that is released by endothelial
cells in blood vessel cell walls; activates
an enzyme in neighboring smooth muscle
cells
G protein coupled receptors
-Plasma membrane receptor that works with the
help of a G?protein (a GTP?binding protein that
relays signals from a plasma membrane signal
receptor.)
� A large family of similar proteins, highly conserved
from yeast to humans.
� Involved in embryonic deve
Receptor tyrosine kinase
� Can trigger more than one signal transduction
pathway at once
� Have an extracellular signal binding site, a
membrane?spanning alpha helix, and cytoplasmic
tyrosine kinase domain(s)
? Kinase: an enzyme that catalyzes the transfer of
phosphate groups
? T
Dimerization
activates the tyrosine?kinase domains, which
add a phosphate from an ATP to a tyrosine on the tail of the
other polypeptide, activating the receptor.
Ion channel receptors
� A type of membrane receptor with a region
that can act as a "gate."
� Particularly important in the nervous system
(for release of neurotransmitters.)
� There are also gated ion channels that are
controlled by electrical signals instead of
ligands (impo
3 Steps of cell communication
-reception
-transduction
-response
Reception
� Signal molecules act as ligands, specifically binding
to their receptors (like a key in a lock or like a
substrate to an enzyme.)
� Binding of the ligand may cause the receptor to
change shape or aggregate.
Transduction
Usually a multiple step pathway.
� Pathway amplifies the signal(binding of a single
ligand results in a large number of activated
molecules at the end of the pathway.)
� Provides multiple steps for regulation and
coordination.
� "Relay molecules" are most
Response
diverse
� E.g., response to the hormone epinephrine
(released from the adrenal glands in response to
physical or mental stress) is the breakdown or
glycogen stores in the liver and skeletal muscle to
glucose?1?P.
How does reception differ between the hydrophilic and hydrophobic chemical messengers?
-hydrophobic chemical messengers are small enough to cross hydrophobic interior of the membrane
-include steriod and thyroid hormones= intracellular responses
-water soluble signaling molecules are hydrophillic and cannot cross plasma membrane
GPCR
-G protein coupled receptor
-cell-surface transmembrane receptor that works with the help of a G protein
-view image on page 211.
Secondary messengers
-many signaling pathways involve small, non-protein, water-soluble molecules or ions
-can readily spread throughout the cell by diffusion
Cyclic AMP
-binding of epinephrine to the plasma membrane of a liver cell elevates the cytosolic concentration of a compound called cyclic adenosine monophosphage... cAMP
-cAMP broadcasts signal to the cytoplasm
-first messenger activates a G protein-coupled recepto
Ca 2+
-even more widely used thatn cAMP as a second messenger
-Used in both G?protein?coupled and receptor
tyrosine kinase pathways.
-Increased calcium ion concentration causes muscle
contraction, secretion of a variety of substances,
and cell division
Maintenance of calcium ion concentration in an animal cell
-concentration in cytosol is normally much lower than the concentration outside the cell
-protein pumps in the plasma membrane and the ER membrane, driven by ATP, move Ca 2+ from the cytosol into the extracellular fluid and into the lumen of the ER
-mitoc
Phosphorylation cascades
-a series of different molecules in a pathway are phosphorylated in turn, each molecule adding a phosphate group to the next one in line
ex:
-a relay molecule activates protein kinase 1
-active protein kinase 1 transfers a phosphate from ATP to an inactiv
Protein phosphatase
an enzyme that catalyzes the
removal of phosphate group from a protein (usually
inactivating the protein.)
Epinephrine
-when secreted as a hormone by the adrenal medulla, mediates "fight-or-flight" reponses to short-term stresses. Also known as adrenaline
What is the cellular response that epinephrine stimulates?
-stimulation of glycogen breakdown by epinephrine
Is it possible for a chemical messenger to produce different cellular responses among different cells?
-Yes
-some kinds of signals responses in both cell but different responses
-ex: liver and heart muscle cell
-epinephrine stimulates liver to break down glycogen
-main response of heart cell to epinephrine is contraction..leading to a more rapid heartbeat
Explanation for specificity exhibited in cellular to responses
-because different kinds of cells turn on different sets of genes, different kinds of cells have different collections of proteins
Signal amplification
-elaborate enzyme cascades amplify the cell's response to a signal
-amplification effect stems from the fact that these proteins persist in the active form long enough to process numerous molecules of substrate before they become inactive again
Result of signal's amplification
a small number of ephineprine molecules binding to receptors on the surface of a liver/muscle cell can lead to the release of hundreds of millions of glucose molecules from glycogen
Scaffolding proteins
-A large relay protein to which
several other relay proteins are simultaneously
attached to increase the efficiency of signal
transduction.
Termination of the signal
-cellular response occurs only when concentration of receptors with bound signaling molecules is aboce a threshold
-when the number of active receptors falls below a certain threshold the cellular response ceases
-if a signaling pathway component becomes
Mechanisms to turn off pathways (turn to inactive forms)
-GTPase activity intrinsic to a G protein hydrolyzes its bound GTP
-the enzyme phosphodieterase converts cAMP to AMP
-protein phosphatases inactivate phosphorylated kinases and other proteins and so forth
-as a result, the cell is soon ready to respond to
Apoptosis
-cell suicide
-cellular agents chop up the DNA and fragment organelles and other cytoplasmic components
-the cell shrinks and becomes lobed
-cell's parts are packaged up in vesicles that are engulfed and digested by specialized scavenger cells, leaving no
Why and how does apoptosis occur?
-embryonic development is a period during which apoptosis is widespread and plays a crucial role
-paw development of mouse..eliminates cells in the interdigital regions, forming fingers
-triggered by signals that activate a cascade of signal proteins in t
Signals that trigger apoptotic pathways
-death signal
-when a cell recieves a death signal, Ced-9 is inactivated, relieving its inhibition of Ced-3 and Ced-4.
-active Ced-3 triggers a cascade of reactions leading to activation of nucleases and other proteases
-action of these enzymes causes cha
What can result from a failure of cell suicide?
-parkinsons and alzherimer's disease
-cancer
What if there was no signal transduction pathway in cell signaling (receptor --> transduction ---> response? How would it affect the cellular response?
-No cellular response
What if there is a mutation in the GTP-binding protein, such that GDP is permanently bound. How would it affect the enzyme? G-protein coupled receptor?
-Enzyme would remain inactive because of no substrate; no effect on receptor
What will be the effect of this mutation (question 3 purple worksheet) on the g-protein coupled receptor? GTP-binding protein? Enzyme?
Receptor will be inactive; GTP-binding protein will be always be bound to GDP
(inactive); enzyme will be inactive.
What will be the effect of a mutation in the active site of the enzyme on G-protein coupled receptor? GTP-binding protein? Cellular response?
No effect; No effect; No cellular response
A mutation in the signaling molecules causes them to irreversibly bind to their receptor. How would it affect the receptor? What would happen to the cellular response?
Constitutively active receptor; continual cellular response
Abnormalities in protein responsible for cellular response 2 abrogate the signaling cascade for cellular response 2. What would be the effect on cellular response 1? How would it affect the receptor?
No effect; No effect
Testosterone is a hormone that binds to an intracelllular receptor. Suppose a drug adds to the hydrophillic functional group to testosterone, how would it affect the interaction of testosterone with its receptor? Cellular transcription?
Testosterone cannot pass the plasma membrane; No transcriptional activation
Consider a mutation in PIP2. What would happen to the production of IP3? What would be the effect on G-protein coupled receptor? Phospholipase C cleaves PIP2 to generate IP3. How would change in PIP2 affect phospolipase C? What would happen to calcium rel
Low to no production of IP3; No effect; No effect; No calcium release by ER;
No cellular response
Opiates are naturally occuring and synthetic alkaloids. The compounds are psychoactive and have and have affinity for their receptor. Naloxones also bind opoid receptors with very high affinity, but have no psychoactive properties. What would be the resul
No cellular response (feeling of pleasure) in either individual.
Since naloxone mimics codeine, it would compete with codeine to bind to opioid
receptor and could be used to counter the overdose effects of opiates.