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CHEM 475 > Chapter 14 > Flashcards

Chapter 14 Flashcards

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1
Q

What is the main function of signal transduction pathways?

A

Signal transduction pathways allow cells to respond to a changing environment.

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2
Q

How do signal transduction pathways function in relation to computer chips?

A

Signal transduction pathways function like computer chips with components that have ON/OFF switches.

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3
Q

What are the six main principles of signal transduction pathways?

A
  1. Release of primary message
  2. Reception of primary message
  3. Intracellular delivery of message
  4. Amplification and transduction of the signal
  5. Alteration of the physiological response
  6. Termination of the signal.
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4
Q

What are secondary signals in the context of signal transduction?

A

Secondary signals, or secondary messengers, are molecules that amplify the primary signal received by a cell and help transduce the signal further into the cell’s compartments

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5
Q

What is PIP2 and its role in signal transduction?

A

PIP2 (phosphatidylinositol 4,5-bisphosphate) is a pro-signal molecule that acts as a precursor for the generation of secondary messengers in signal transduction.

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6
Q

How do secondary messengers facilitate crosstalk in signal transduction pathways?

A

The use of common secondary messengers allows different signal transduction pathways to interact and influence each other, enabling crosstalk between pathways

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7
Q

What triggers the release of the primary signal epinephrine?

A

The primary signal epinephrine is released by the adrenal glands in response to stress or physical activity, acting as a hormone that prepares the body for a ‘fight or flight’ response.

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8
Q

Explain the significance of amplification in signal transduction pathways.

A

Amplification is significant in signal transduction pathways because it allows a small number of primary signals to produce a large response in the target cell, ensuring robust physiological changes.

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9
Q

What is the physiological response alteration in signal transduction pathways?

A

The alteration of physiological response refers to the changes in cell activities and functions that occur as a result of the signal transduction process, impacting processes like metabolism, growth, and immune response.

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10
Q

What is meant by the termination of the signal in signal transduction pathways?

A

Termination of the signal involves mechanisms that deactivate or remove the signal to prevent overreaction or continuous activation of the pathways, ensuring that the cellular response is appropriately regulated.

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11
Q

What are the effects of epinephrine (adrenaline) release in stressful situations?

A

Increased concentration of glucose in the blood by promoting glycogenolysis and gluconeogenesis

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11
Q

What structural features characterize the 7TM receptor?

A

It is a single protein embedded in the plasma membrane, detecting unique ligands and undergoing conformational changes upon ligand binding.

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12
Q

What does conformational changes of 7TM activate?

A

G-proteins

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13
Q

What are the functions of G-proteins in relation to 7TM receptors?

A

G-proteins, which are heterotrimeric (composed of three different subunits), are kept in an inactive state. When a 7TM receptor is activated by a ligand, it induces a conformational change leading to the activation of G-proteins. The beta and gamma subunits dissociate allowing the alpha subunit to exchange GDP for GTP, activating signaling pathways.

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14
Q

What is the role of cAMP in cell signaling?

A

cAMP binds to protein kinase A (PKA) and activates its kinase activity. Activated PKA phosphorylates multiple downstream targets, amplifying the original signal.

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15
Q

What happens after G-proteins are activated?

A

Once activated, the G-s protein (the stimulatory G-protein) activates adenylate cyclase, which converts ATP to cyclic AMP (cAMP), a secondary messenger.

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16
Q

What is adenylate cyclase?

A

Adenylate cyclase is an enzyme that converts ATP (adenosine triphosphate) to cAMP (cyclic adenosine monophosphate), a secondary messenger involved in signal transduction.

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17
Q

What is the effect of low levels of epinephrine on cAMP?

A

The detection of low levels of epinephrine results in a large increase in cAMP levels due to the activation of adenylate cyclase.

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18
Q

How does cAMP activate PKA?

A

cAMP binds to protein kinase A (PKA), leading to a conformational change that activates its kinase activity, allowing PKA to phosphorylate various target proteins.

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19
Q

What happens to G-proteins after they activate adenylate cyclase?

A

After activating adenylate cyclase, G-proteins self-deactivate by hydrolyzing the bound GTP to GDP, which changes their conformation and prevents further interactions with adenylate cyclase.

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20
Q

What are the two mechanisms that deactivate the receptor after stimulation by epinephrine?

A
  1. Epinephrine dissociates from the receptor, turning it OFF.
  2. GRK2 phosphorylates serine and threonine residues in the receptor’s C-terminus, leading to the binding of arrestin which blocks G-protein binding.
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21
Q

What role does GRK2 play in receptor deactivation?

A

GRK2 (G-protein coupled receptor kinase 2) phosphorylates specific serine and threonine residues in the receptor’s C-terminus, which promotes the binding of arrestin that prevents G-protein activation.

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22
Q

What is the function of PDE in relation to cAMP?

A

Phosphodiesterase (PDE) hydrolyzes cAMP into AMP, effectively reducing the levels of cAMP within the cell and contributing to the termination of the signaling pathway.

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23
Q

What is feedback inhibition by PKA?

A

Feedback inhibition by PKA (protein kinase A) occurs when the products of a signaling pathway (after sufficient PKA activation) inhibit upstream signaling components to prevent excessive signaling.

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24
What role does PDE play in cAMP signaling?
PDE (phosphodiesterase) is an enzyme that breaks down cAMP (cyclic adenosine monophosphate), leading to the cessation of cAMP signaling.
25
What does PKA phosphorylate, and what is the significance of this action?
PKA (protein kinase A) phosphorylates GRK2 (G-protein coupled receptor kinase 2), which activates GRK2 to further regulate signaling pathways.
26
What is the effect of GRK2 phosphorylating the epinephrine receptor?
The phosphorylation of the epinephrine receptor by GRK2 results in its deactivation, thus terminating the signaling pathway associated with epinephrine.
27
What is the phosphoinositide cascade, and why is it referred to as having 'two for one' signals?
The phosphoinositide cascade is a signaling pathway in which a signal leads to the production of two secondary messengers, DAG (diacylglycerol) and IP3 (inositol trisphosphate), from PIP2 (phosphatidylinositol 4,5-bisphosphate). This mechanism allows for simultaneous signaling through multiple pathways.
28
How does angiotensin II influence blood pressure?
Angiotensin II is a peptide hormone that plays a crucial role in regulating blood pressure through its action on blood vessels. It constricts blood vessels and stimulates the release of aldosterone, leading to increased blood volume and elevated blood pressure.
29
What type of receptor binds angiotensin II, and what intracellular pathway is activated?
Angiotensin II binds to a 7-transmembrane receptor (7TM receptor), which activates the G protein isoform Gq, initiating a signaling cascade.
30
What is the role of phospholipase in angiotensin II signaling?
Phospholipase is activated by the Gq protein and catalyzes the cleavage of the phospholipid PIP2, producing DAG and IP3, which serve as secondary messengers.
31
What is the fate of DAG and IP3 after PIP2 is cleaved?
After PIP2 is cleaved, DAG remains in the membrane and activates protein kinase C (PKC), while IP3 diffuses into the cytoplasm and triggers the release of calcium from the endoplasmic reticulum (ER).
32
Describe the role of calcium in the signaling pathway involving PKC.
Calcium acts as an important secondary messenger. It is released from the ER into the cytoplasm, where it binds to calmodulin (CaM), allowing the complex to activate PKC. Activated PKC then phosphorylates target proteins on serine and threonine residues, leading to a variety of cellular responses.
33
What is calmodulin (CaM) and how does it function?
Calmodulin (CaM) is a calcium-binding messenger protein that has four binding sites for calcium ions. It acts as a calcium sensor, mediating various downstream effects by binding to and activating target enzymes in response to changes in intracellular calcium levels.
34
Explain the mechanism by which active PKC exerts its effects.
Active PKC, after forming a complex with calcium and DAG, is recruited to the membrane. There, it phosphorylates serine and threonine residues on target proteins, leading to alterations in their activity and mediating various cellular responses.
35
What is the significance of calcium as a secondary messenger in cellular signaling?
Calcium is a versatile secondary messenger that regulates many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and cell growth. Its levels in the cytoplasm are tightly regulated and its signaling pathways are crucial for normal cellular function.
36
What is the role of calcium in the activation of calmodulin (CaM)?
Calmodulin (CaM) is activated when calcium (Ca) levels reach 500 nM. The EF hand motif in CaM is a calcium-binding site that undergoes extensive conformational changes upon binding, allowing active CaM to interact with target proteins.
37
What is the mechanism by which CaM kinase is activated?
Active calmodulin (CaM) binds to CaM kinase, which induces conformational changes in the kinase, leading to its activation.
38
Describe the insulin signaling pathway.
The insulin signaling pathway is initiated by insulin, a peptide hormone released in response to increased blood glucose levels. The pathway involves the activation of a receptor tyrosine kinase (RTK) comprised of two subunits linked by a disulfide bond.
39
What does the insulin receptor consist of?
The insulin receptor is composed of two subunits linked by a single disulfide that form the insulin binding site. Two α-subunits form the insulin binding site while the beta subunit possesses intracellular kinase activity, which is maintained in an inactive state due to an activation loop.
40
What is Insulin Receptor Substrate 1 (IRS-1)?
IRS-1 is an adaptor protein in the insulin signaling pathway that interacts with the insulin receptor. It recognizes phosphatidylinositol 4,5-bisphosphate (PIP2) using a pleckstrin homology (PH) domain and phosphotyrosines through SH2 domains.
41
What modifications occur to IRS-1 upon its activation in the insulin signaling pathway?
Upon activation, IRS-1 is phosphorylated by the receptor tyrosine kinase (RTK) at four different YXXM sequences, which are critical for downstream signal transduction.
42
What is the role of phosphoinositide 3-kinase (PI3K) in the insulin signaling pathway?
Phosphoinositide 3-kinase (PI3K) binds to the phosphorylated tyrosine residues on IRS-1, playing a significant role in transmitting the insulin signal further downstream.
43
Explain the significance of SH2 domains in IRS-1.
SH2 (Src Homology 2) domains are important for the binding of specific phosphotyrosines on IRS-1, allowing it to interact with signaling proteins that initiate further steps in the insulin signaling cascade.
44
How does PDK1 contribute to cellular signaling?
PDK1, upon being recruited to the membrane by PIP3, activates kinase activity, subsequently activating another kinase called Akt, which is important for various cellular functions.
45
What is the significance of Akt in cellular signaling?
Activated Akt can move throughout the cell and phosphorylate proteins that are essential for processes such as glycogen synthesis and glucose uptake.
46
How is the signaling process involving Akt terminated?
The signaling process is terminated by the action of phosphatases, which dephosphorylate the signaling molecules.
47
What is the role of Epidermal Growth Factor (EGF) in cellular signaling?
EGF stimulates the growth of epithelial cells and is crucial for cell proliferation and differentiation.
48
What type of receptor is the EGF receptor and how does it function?
The EGF receptor is a receptor tyrosine kinase (RTK) that binds to EGF, leading to dimerization of the receptors and cross-phosphorylation at the C-terminus.
49
What is Grb2 and what is its role in EGF signaling?
Grb2 is an adaptor protein that contains one SH2 domain and two SH3 domains. It binds to Sos exchange factor to facilitate the activation of Ras.
50
Explain the function of Ras in signaling pathways.
Ras is a small GTP-binding protein that acts as a crucial control protein in signaling pathways, particularly in the exchange of GDP for GTP facilitated by Sos.
51
How does Sos influence the activity of Ras?
Sos opens the binding site of Ras to facilitate the exchange of GDP for GTP, activating Ras.
52
Name some components of the mitogen-activated protein kinase (MAPK) cascade involved in EGF signaling.
Important components of the MAPK cascade include MEK and ERK.
53
What are the implications of defects in signaling pathways?
Defects in signaling pathways can lead to uncontrolled cell growth and progression of cancer.
54
Define cancer in the context of cell signaling.
Cancer is characterized by uncontrolled cell growth, often resulting from failures in normal signaling pathways.
55
What is the significance of wild type c- in cancer signaling?
Wild type c- typically refers to the normal, non-mutated form of signaling proteins which play a critical role in maintaining normal cell functions; mutations can lead to uncontrolled proliferation.
56
What happens to Src when it is phosphorylated on a C-terminus Tyrosine?
Src turns off when phosphorylated on a C-terminus Tyrosine.
57
What is v-Src and how does it relate to c-Src?
v-Src is a viral homolog of the host protein c-Src, and it is an expressed oncoprotein that does not have a regulatory Tyrosine, making it always active.
58
In terms of classification, how is c-Src categorized?
c-Src is classified as a proto-oncogene.
59
What common mutation occurs in Ras that is associated with cancer?
The most common mutation in Ras stops GTP hydrolysis, which leaves Ras always ON.
60
What is the role of tumor-suppressor genes in cancer?
Tumor-suppressor genes lead to cancer when they are inactivated.
61
What is the function of BRCA2 in the cell?
BRCA2 is expressed in breast tissues and helps repair damaged DNA; if necessary, it triggers apoptosis.
61
Give an example of a tumor-suppressor gene and its associated role in cancer.
MAP phosphatases are an example of tumor-suppressor genes; their inactivation can contribute to cancer.
62
What role does the bcr-abl gene play in Chronic Myeloid Leukemia (CML)?
The bcr-abl gene behaves like an unregulated Abl kinase and is present in 90% of patients with Chronic Myeloid Leukemia.
63
What is Gleevec (imatinib) and its significance in cancer treatment?
Gleevec (imatinib) specifically inhibits the bcr-abl kinase, providing targeted therapy for Chronic Myeloid Leukemia.
64
How can antibodies be utilized in cancer treatment?
Antibodies can be used to target receptors involved in cancer.
65
What are odorant receptors (ORs) and their function in the olfactory system?
Odorant receptors (ORs) are a large family of G-protein-coupled receptors located in the olfactory epithelium of the nasal cavity. They are responsible for detecting airborne odor molecules and are crucial for the sense of smell. Each OR can bind to specific odorant molecules.
66
Why are odorant shapes important for recognition by odorant receptors?
Odorant shapes are important because they determine how well different odorant molecules fit into the binding site of specific ORs. The interaction between the shape of the odorant and the receptor is fundamental to the recognition of distinct smells, enabling the ability to discriminate between different odors.
67
How many different human odorant receptors are known?
There are approximately 400 different human odorant receptors (ORs) identified.
68
Do olfactory neurons express more than one type of odorant receptor?
No, each olfactory neuron expresses only one type of odorant receptor. This specificity allows for the discrimination of a wide variety of odorants through the activation of different patterns of ORs.
69
What occurs in the neuron when cAMP activates non-specific ion channels?
When cAMP activates non-specific ion channels in olfactory neurons, sodium (Na+) and calcium (Ca2+) ions enter the neuron, causing depolarization. This depolarization triggers action potentials, transmitting the signal to the brain for odor perception.
70
What results from different odorants interacting with odorant receptors?
Different odorants result in distinct patterns of activation of the odorant receptors, which the brain interprets as various smells. This pattern recognition is critical for identifying and distinguishing between a wide range of odors.
71
What is the function of Rhodospin?
Rhodopsin is a light-sensitive protein found in the rod cells of the retina, acting as the primary photoreceptor molecule responsible for converting photons of light into electrical signals that trigger the process of vision, particularly in low-light conditions
72
Rhodopsin in rods contains cis-retinal that absorbs at ____ mm
500
73

CHEM 475 (4 decks)

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