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Module 1B > 14 Cellular Signaling > Flashcards

14 Cellular Signaling Flashcards

1
Q

T or F: Cell to cell signaling is also called intracellular communication.

A

False. It should be intercellular communication.

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2
Q

What are the four main types of chemical messengers?

A

Endocrine, Paracrine, Autocrine, Neurocrine

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3
Q

T or F: Some of the chemical mediators act as more than one type of chemical messengers.

A

True.

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4
Q

Give one example of an endocrine messenger.

A

Insulin / Growth hormones

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5
Q

Endocrine messengers are also known as ___________.

A

Classical hormones

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6
Q

T or F: Paracrine messengers act on distant cells.

A

False. Paracrine messengers act locally to affect nearby, target cells, not distant ones.

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7
Q

Through what medium do paracrine messengers diffuse?

A

Interstitial fluid or ECF

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8
Q

Which messenger is typically involved in long-distance signaling?

A

Endocrine

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9
Q

What is the speed of transport for endcorine messengers: fast or slow?

A

Slow

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10
Q

What specialized structure allows direct communication between neighboring cells in juxtacrine signaling?

A

Gap junctions

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11
Q

What is another name for juxtacrine messengers?

A

Local hormones

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12
Q

T or F: Noradrenaline only functions as a neurotransmitter.

A

False. Noradrenaline functions both as a neurotransmitter and as a classical hormone.

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13
Q

What dual roles can dopamine play in the body?

A

Neurotransmitter and a hormone

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14
Q

What is another term for autocrine messengers?

A

Intracellular chemical mediators

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15
Q

How do endocrine messengers reach their target cells?

A

Bloodstream

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16
Q

Leukotrienes are an example of paracrine messengers.

A

False. Leukotrienes are an example of autocrine messengers.

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17
Q

What are neurocrine substances also known as?

A

Neural Messengers

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18
Q

An endogenous signaling molecule that carries information from one nerve cell to another nerve cell, muscle, or another tissue

A

Neurotransmiter

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19
Q

Name two examples of neurotransmitters.

A
  • Acetylcholine
  • Dopamine
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20
Q

Chemical substances released by nerve cells directly into the blood and transported to distant target cells.

A

Neurohormones

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21
Q

Give examples of neurohormones

A
  • Oxytocin
  • ADH
  • Hypothalamic releasing hormones
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22
Q

What is the primary function of receptors in neurocrine signaling?

A

To sense and respond to changes in signals by activating biochemical pathways within the cell, leading to a defined response.

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23
Q

What are chemical mediators and receptors?

A

Protein molecules to which a chemical messenger binds to stimulate a cell response

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24
Q

Where are receptors located?

A

On the surface of the cell, within the cytoplasm, or in the nucleus.

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25
Q

Neurotransmitters are released at synaptic junctions from nerve cells and act across a narrow synoptic cleft on a post synaptic cell

A

Neural/Synaptic

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26
Q

How do hormones and growth factors reach their target cells in endocrine communication?

A

Through circulating blood or lymph.

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27
Q

What is the difference between paracrine and autocrine communication?

A
  • In paracrine communication, the product of cells diffuses in the extracellular fluid (ECF) to affect neighboring cells
  • in autocrine communication, the chemical
    messenger binds to receptors on the same cell that secreted it.
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28
Q

Name types of chemical messengers that can function as neurotransmitters and paracrine mediators

A

Amines, amino acids, and steroids

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29
Q

What are the specialized junctions that allow intracellular signaling molecules to diffuse from the cytoplasm to one cell to an adjacent cells?

A

Gap Junctions

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30
Q

Where are gap junctions found?

A

Cardiac and smooth muscles

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31
Q

What are the specialized junctions that allows cells to be electrically coupled or permit rapid propagation of electrical activity, which is vitally important for the coordinated activity of cardiac and smooth muscles?

A

Gap Junctions

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32
Q

In neural communication, what are released at the synapse?

A

Neurotransmitters

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33
Q

What kind of communication utilizes neurotransmitters wherein the signal may travel long distances however the effect is limited to a very specific area?

A

Neural Communication

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34
Q

What kind of communication has a relatively slow due to time required for diffusion and the blood flow to reach the target cell?

A

Endocrine Communication

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35
Q

What does endocrine communication utilize to convey the signal?

A

Hormones

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36
Q

What kind of communication involves the secretion of chemicals into the interstitial fluid and primarily affects local areas or nearby cells?

A

Paracrine Communication

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37
Q
  1. In Paracrine communication, where are the chemicals secreted?
A

Interstitial fluid

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38
Q

What are specialized junctions allowing intracellular signaling molecules to diffuse from a cell’s cytoplasm to its adjacent cell.

A

Gap junctions

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39
Q

Why are gap junctions found in cardiac cells and smooth muscles?

A

Theey can rapidly propagate electrical activity from cell to cell which is important for coordinated activity of cardiac and smooth muscles

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40
Q

Gap junctions can be found in which cells?

A

Cardiac muscles and smooth muscles

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41
Q

T or F: As molecules go from one cell to another through gap junctions, they pass freely through the ECF.

A

False. They pass freely between cells WITHOUT entering the ECF.

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42
Q

Give some examples of substances that can pass via gap junctions.

A

-Ions
-Sugars
-Amino acid
-Other solutes within required molecular weight

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43
Q

In neural communication, at what site are neurotransmitters released?

A

Synapse

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44
Q

T or F:
1) Synaptic signaling is extremely fast or in milliseconds
2) Given its speed, the signal can travel only short distances.

A

1) True
2) False. It can travel LONG distances.

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45
Q

What characteristic of neural communication defines it as limited to a very specific area.

A

Discrete

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46
Q

In endocrine communication, the signaling molecules are released where?

A

Bloodstream, blood, lymph

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47
Q

Aside from signaling molecules, endocrine communication can also release?

A

Growth factors

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48
Q

Give an example of discrete or generalized hormone.

A

Antidiuretic hormone (ADH) or Vasopressin

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49
Q

T or F: The effect of endocrine communication is slow and short.

A

False. It is slow but prolonged

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50
Q

1) What is the type of communication if secreted chemicals affect local or nearby cells?
2) How about if it affects the same cell releasing it?

A

1) Paracrine communication
2) Autocrine communication

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51
Q

What are the 4 steps involved in cell signaling and signal transduction?

A
  1. Recognition
  2. Transduction
  3. Transmission
  4. Response
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52
Q

The receptor to which a signaling molecule binds to can be located in?

A

-Plasma membrane
-Cytoplasm
-Nucleus

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53
Q

In recognition, upon binding of a ligand to a receptor, what are activated? Cite some examples.

A

Intracellular proteins (i.e. kinases, phosphatases, GTP-binding proteins)

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54
Q

The signaling proteins interact with? What is their effect on them?

A

Target proteins; Regulate their activity

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55
Q

What are the functions of signaling molecules?

A

1) Regulate cell growth, division, and differentiation
2) Influence cellular metabolism
3) Modulate intracellular ionic composition
4) Control cytoskeleton-associated events (cell shape, division, migration)
5) Control adhesion (cell-to-cell and cell-to-matrix)

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56
Q

How do signaling molecules modulate the ionic composition intracellularly?

A

Regulating activity of ion channels and transport proteins

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57
Q

The recognition of chemical messengers or signal molecules or ligands by cells typically begins by _______

A

interaction or binding with a receptor at that cell

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58
Q

Which serve as cellular switches during recognition?

A

receptors

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59
Q

T or F. Receptors are static components of the cell.

A

False (receptors are not static components)

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60
Q

What do you call the type of regulation wherein there is an increase in the number of receptors when chemical messenger is deficient?

A

Up-regulation

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61
Q

What do you call the type of regulation wherein there is a decrease in the number/activity of receptors when chemical messenger is in excess.

A

Down-regulation

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62
Q

For receptors in the membrane, ______ is responsible for down regulation.

A

receptor-mediated endocytosis

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63
Q

In receptor-mediated endocytosis, when ligands bind to their receptors, what do they form?

A

ligand-receptor complexes

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64
Q

T or F. In receptor-mediated endocytosis, ligand-receptor complexes move internally in the membrane to coated bits

A

False (Ligand-receptor complexes move LATERALLY in the membrane to coated bits)

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65
Q

What do you call the process wherein the coated bits during receptor-mediated endocytosis are subjected to endocytosis to enter the cell?

A

Internalization

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66
Q

Some receptors are either ____ after internalization or ____ by de Novo synthesis in the cell.

A

recycled; replaced

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67
Q

When there is hormone or neurotransmitter in excess, number of active receptors increases or decreases?

A

decreases

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68
Q

When there is deficiency of chemical messengers, the number of active receptors increases or decreases?

A

increases

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69
Q

This is a type of down-regulation, wherein receptors are chemically modified to become less responsive.

A

Desensitization

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70
Q

What are the four major types of receptors according to their intracellular signaling pathways?

A

Ion Channel-Linked Receptors, G-Protein Coupled Receptors, Enzyme-Linked/Catalutic Receptors, Nuclear Receptors

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71
Q

Neurotransmitters directly gating ion channels.

A

Ionotropic receptors

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72
Q

Examples of neurotransmitters.

A

Acetylcholine and Norepinephrine

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73
Q

Examples of this receptor include Nicotinic cholinergic receptor.

A

Ligand-gated ion channels/Ion Channel-Linked Receptors

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74
Q

Examples of this receptor include K+ channel.

A

Ligand-gated ion channels/Ion Channel-Linked Receptors

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75
Q

Examples of this receptor include transient receptor potential cation channel vanilloid member 1 (TRPV1).

A

Ligand-gated ion channels/Ion Channel-Linked Receptors

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76
Q

This receptor mediate direct and rapid signaling between electrically excitable cells.

A

Ligand-gated ion channels/Ion Channel-Linked Receptors

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77
Q

What signaling molecules bind to receptors that cause the opening and closing of ion channels?

A

Neurotransmitters

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78
Q

True or False: Binding of neurotransmitters changes ionic permeability of plasma membrane as well as its membrane potential.

A

TRUE

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79
Q

True or False: The selectivity of Ion Channel-Linked receptor depends on diameter, shape, electrical charges, and chemical bonds along its inside surface.

A

TRUE

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80
Q

[From Book Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 146, Pgs. 574-575] A type of ion channels in the postsynaptic neuronal membrane which usually allow sodium ions to pass when opened (also sometimes allow K+ and/or Ca+).

A

Cation channel

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81
Q

[From Book Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 146, Pgs. 574-575] A type of ion channels in the postsynaptic neuronal membrane which mainly allow chloride ions to pass.

A

Anion channel

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82
Q

[From Book Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 146, Pgs. 574-575] A type of ion channels in the postsynaptic neuronal membrane which are lined with negative charges to attract the positively charged molecules.

A

Cation channel

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83
Q

[From Book Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 146, Pgs. 574-575] A neurotransmitter that opens cation channels (allow positively charges ions) and excite the neuron.

A

Excitatory transmitter

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84
Q

[From Book Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 146, Pgs. 574-575] A neurotransmitter that opens anion channels (allow negatively charges ions) and inhibit the neuron.

A

Inhibitory transmitter

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85
Q

GPCR downstream target proteins that regulate signaling pathways if the target protein is an?

A

Enzyme

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86
Q

GPCR change membrane ion permeability if target protein is an?

A

ion channel

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87
Q

What is the largest and most diverse group of membrane receptors?

A

G-Protein coupled receptors

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88
Q

other names of G-PCR

A

seven-transmembrane receptor, hepta-helical receptors, seven-helix receptore, serpentine receptors

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89
Q

type of receptor that is targeted in drug discovery

A

G-Protein coupled receptors ( because the cell surface receptors act like an inbox for messages in the form of light energy, peptides, lipids, sugars, and proteins making it diverse)

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90
Q

GPCR binds extracellular substances and transmits signals to an intracellular molecule called?

A

G-Protein (guanine nucleotide binding protein)

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91
Q

Name the subunits of G-proteins.

A

ɑ-subunit , β-subunit, 𝛾-subunit

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92
Q

site for attachment of GDP

A

ɑ-subunit

93
Q

subunit of GPCR that are attached to membrane

A

ɑ and 𝛾-subunit

94
Q

What are the subunits of a G-protein? (inactive state)

A

Alpha (ɑ), Beta (β), and Gamma (𝛾)

95
Q

What does the three G-protein subunits form?

A

Complex

96
Q

What does GDP stand for?

A

Guanosine diphosphate

97
Q

What does GTP stand for?

A

Guanosine triphosphate

98
Q

How does the G-protein becomes activated?

A

Through the binding of a ligand to a GPCR, and once the GDP is released for the binding of GTP

99
Q

Which among the 3 G-protein subunits separates or travels away from the other 2?

A

The alpha subunit

100
Q

What are the two G-protein subunits that form a signaling molecule together?

A

The beta and gamma subunits

101
Q

What is the significance of the alpha subunit of a G-protein, especially when activated?

A

The conversion of GTP to GDP by the alpha subunit.

102
Q

Describe the process of how a GPCR works, including their subunits.

A

A. The G-protein is inactive, wherein the three subunits form a complex, binding GDP to the alpha subunit. B. To reach an active state, a ligand must bind to the GPCR, followed by the conversion of the GDP to GTP by the alpha subunit. C. The alpha subunit then separates from the combined beta and gamma subunits, which can cause or bring many biological effects. D. The two subunits form together a signaling molecule, which can also activate a variety of effectors. The process repeats the activation and inactivation process, where the alpha subunit converts GTP to GDP and returns to the two subunits.

103
Q

True or False: All receptors when activated function directly as enzymes or are closely associated with enzymes that they activate.

A

False: Not all, but only some.

104
Q

What are the proteins that pass through the membrane only once in contrast to the seven transmembrane GPCRs?

A

Enzyme-linked receptors

105
Q

What are the most common enzyme-linked receptors?

A

Protein kinases or those that are associated with protein kinases.

106
Q

What causes the kinase to phosphorylate a specific subset of proteins on specific amino acids?

A

Ligand binding

107
Q

True or False: Ligands can only activate protein activity.

A

False: Ligands can either activate or inhibit the protein activity.

108
Q

True or False: Enzyme-linked receptors are proteins that can pass through the membrane multiple times/

A

False: Enzyme-linked receptors can only pass through once.

109
Q

What are enzyme-linked receptors composed of?

A

Hormone-binding sites outside the cell membrane and catalytic/enzyme-binding sites inside

110
Q

True or False: Many enzyme-linked receptors have extrinsic enzyme activity.

A

False: Many enzyme-linked receptors have intrinsic enzyme activity.

111
Q

Hormone receptors inside the cell where adrenal and gonadal steroid hormones, thyroid hormones, retinoid hormones, and vitamin D bind to rather than in the cell membrane.

A

Nuclear Receptors

112
Q

Ligands that interact with cytoplasmic receptors.

A

Glucocorticoids and Mineralocorticoids

113
Q

Ligands that interact with nuclear receptors.

A

Estrogen, Progesterone, and Thyroid Hormones

114
Q

The activated hormone receptor complex binds to a specific regulatory or promoter sequence of the DNA called __________ which either activates or represses specific chains of mRNA.

A

Hormone Response Element

115
Q

An __________ can activate a gene response only if the appropriate combination of gene regulatory proteins is present.

A

Intracellular Receptor

116
Q

The process within cells that converts one type of signal or stimulus into another.

A

Signal Transduction

117
Q

Signal transduction allows a cell to change its behavior in response to ___________ interactions.

A

Receptor-Ligand

118
Q

The molecule that initially binds to the receptor, triggering the signal transduction process.

A

Primary Messengers

119
Q

Intracellular mediators that amplify the response and relay the signal from one part of the cell to another, such as from the plasma membrane to the nucleus, leading to a cascade of cellular events.

A

Secondary Messengers

120
Q

When acetylcholine binds, these channels increase Na+ permeability, altering the membrane potential and enabling the transmission of electrical signals between excitable cells.

A

Ion-Channel Activation

121
Q

A ligand binds to an ion channel, causing it to open and allow ions to pass through, relaying signals. This process is crucial in neural synapses for generating action potentials.

A

Acetylcholine-Gated Na+ Channel

122
Q

What is likely the major site where the anesthetic agents and ethanol exert their effects?

A

What is likely the major site where the anesthetic agents and ethanol exert their effects?

123
Q

Which ion channel is specifically affected by gamma-aminobutyric acid (GABA) and is an NMDA receptor or N-methyl-D-aspartate receptor?

A

The GABA-gated Cl- channel

124
Q

How do anesthetic agents and ethanol cause CNS depression?

A

By altering the functions of ion channels, modifying the electrical activity of neurons through depolarization or hyperpolarization.

125
Q

How do ion channel receptors transduce a chemical signal into a response?

A

By converting a chemical signal into an electrical signal that elicits a certain response in neurons.

126
Q

What happens when G proteins are bounded to a receptor?

A

They may either be stimulated or inhibited

127
Q

What do G proteins interact with after being activated?

A

Different effector proteins or enzymes that catalyze the production of second messengers.

128
Q

What are second messengers, and what is their role?

A

Second messengers are intracellular signals that affect other intracellular proteins, causing a cascade of events.

129
Q

Besides interacting with effector proteins, what else can G proteins interact with?

A

G proteins may also interact with nearby ion channels.

130
Q

G-protein will interact with other effector proteins to produce what?

A

Secondary messengers are intracellular signals that affect other intracellular proteins, causing a cascade of events

131
Q

In its inactive state G-protein (specifically the ɑ- subunit) is bound to what molecule?

A

GDP (Guanosine Diphosphate)

132
Q

Ligand binding to GPCR will cause a conformational change in the heterotrimeric complex, which will promote the release of what?

A

GDP (Guanosine Diphosphate) will be released by the ɑ- subunit, and it will be replaced by GTP (Guanosine Triphosphate)

133
Q

When a ligand binds to GPCR, GDP will be replaced by what molecule?

A

GTP (guanosine triphosphate)

134
Q

What facilitates the dissociation of GDP and binding of GTP in G-proteins

A

GEFs (Guanine exchange factors)

135
Q

Binding of GTP to G-protein will cause this subunit to dissociate from the rest of the subunits?

A

ɑ- subunit

136
Q

The β- and ɑ- subunits of G-protein will regulate what?

A

Downstream effectors (altered activity of enzymes and ion channels)

137
Q

What will inactivate/terminate downstream effectors?

A

Hydrolysis of GTP bound to ɑ-subunit to GDP

138
Q

What facilitates Hydrolysis of GTP bound to ɑ-subunit

A

Regulator of G-protein signalling (RGS protein)

139
Q

What is the most common downstream effector which facilitates conversion of ATP to cAMP?

A

Camp-dependent pathway/adenyl cyclase pathway

140
Q

In the activation of Adenylyl Cyclase, a ligand binds to a receptor that interacts with the alpha G protein composed of:

A

An alpha subunit of the As class

141
Q

What happens when Adenylyl Cyclase is activated?

A

Increases cAMP and activated Protein Kinase A

142
Q

In the inhibition of Adenylyl Cyclase, a ligand binds to a receptor that interacts with a G protein composed of:

A

An alpha subunit of the AI class

143
Q

What happens when Adenylyl Cyclase is inhibited?

A

Decreases cAMP and decreases Protein Kinase A

144
Q

What does cAMP do?

A

Activation of Protein Kinase A and Activation of Cyclic Nucleotide-Gated Ion Channels

145
Q

Adenylyl Cyclase Pathway 2nd Messenger:

A

cAMP

146
Q

What happens when Protein Kinase A is activated?

A

Catalyze Phosphorylation of Proteins, Phosphorylates CREB (cAMP Response Element -Binding) in nucleus

147
Q

When happens when phosphorylation of proteins is catalyzed?

A

Stimulation/Inhibition of Enzymes

148
Q

What happens when CREB (cAMP Response Element -Binding) in the nucleus is phosphorylated?

A

Transcription of genes is regulated

149
Q

Phosphodiester pathway regulates:

A

Phototransduction

150
Q

When light hits the photoreceptor, the light absorbing retinal portion of the rhodopsin is activated that stimulates the:

A

Transducin

151
Q

What does Transducin do?

A

Activates GMP Phosphodiesterase

152
Q

When Transducin activates the GMP Phosphodiesterase, it catalyzes what reaction?

A

Degradation of cyclic GMP into five GMP

153
Q

Reduction of cyclic GMP causes closure of:

A

Sodium channels

154
Q

Reduction of cyclic GMP causes closure of the sodium channels which causes:

A

hyperpolarization of the photoreceptors

155
Q

Phosphodiesterase Pathway 2nd Messenger:

A

cGMP

156
Q

What are the functions of cGMP as a 2nd messenger in the Phosphodiester Pathway?

A

cGMP-Regulated Ion Channels and Activates cGMP-Dependent Kinase

157
Q

What does cGMP-Regulated Ion Channels do?

A

Alters membrane Permeability to Ions

158
Q

When cGMP-Dependent Kinase is activated:

A

Enzymes are stimulated/inhibited

159
Q

A family of enzymes that modulate a variety of signaling pathways.

A

Phospholipase

160
Q

An enzyme that converts phosphatidylinositol biphosphate to inositol triphosphate and diacylglycerol.

A

PLC

161
Q

____diffuses to the endoplasmic reticulum (ER) and activates calcium channels, leading to the release of calcium into the cytosol.

A

InsP3, Inositol triphosphate

162
Q

____activates protein kinase C, which phosphorylates effector proteins, changing their catalytic activities leading to cellular responses.

A

DAG, Diacylglycerol

163
Q

An enzyme that releases arachidonic acid from membrane phospholipids.

A

Phospholipase A2

164
Q

What mediates platelet aggregation, causes airway constriction, and induces inflammation?

A

Prostaglandins

165
Q

In addition to prostaglandins, what else induces platelet aggregation and constricts blood vessels?

A

Thromboxanes

166
Q

What inhibits platelet aggregation and dilates blood vessels?

A

Prostacyclins

167
Q

In a second pathway of arachidonic acid metabolism,_____ initiates the conversion of arachidonic acid
to leukotrienes.

A

5-lipoxygenase

168
Q

____ participates in allergic and inflammatory responses, including those that cause asthma, rheumatoid arthritis, and inflammatory bowel disease.

A

Leukotrienes

169
Q

Ligand binding to GPCRs can also activate____.

A

Phospholipase A2

170
Q

What iniatiates the third pathway of arachidonic acid metabolism?

A

Epoxygenase

171
Q

T or F: Cells coordinate and integrate external chemical signals, including hormones, neurotransmitters, growth factors, and products of cellular metabolism, that serve as chemical messengers and provide cell-to-cell communication

A

TRUE

172
Q

T or F: Signals do not interact with receptors located in the plasma membrane, cytoplasm, and nucleus

A

FALSE

173
Q

An enzyme that facilitates the production of hydroxyeicosatetraenoic acid (HETE) and cis-epoxyeicosatrienoic acid (EETs).

A

epoxygenase

174
Q

These are classes of receptors that have catalytic activity or associated with proteins that have catalytic activity?

A

Catalytic Receptor

175
Q

Which class of receptors is associated with Atrial Natriuretic Peptide and Nitric Oxide?

A

Receptor Guanylyl Cyclase

176
Q

What class of receptor is associated with Transforming Growth Factor-β (TGF-β)?

A

Receptor Threonine/Serine Kinases

177
Q

Name three signaling molecules that utilize Receptor Tyrosine Kinase.

A

Epidermal Growth Factor (EGF), Platelet Derived Growth Factor, Insulin

178
Q

Which receptor class is associated with Interleukin signaling?

A

Tyrosine Kinase Associated Receptors

179
Q

What is the primary action of Receptor Guanylyl Cyclase?

A

It catalyzes the conversion of GTP to cGMP.

180
Q

What does cyclic GMP activate, and what is the result of this activation?

A

Cyclic GMP activates cyclic GMP-dependent protein kinase (PKG), which phosphorylates proteins on specific serine and threonine residues.

181
Q

How does Atrial Natriuretic Peptide (ANP) affect the kidney and blood vessels?

A

ANP inhibits sodium and water reabsorption by the collecting ducts in the kidney, dilates blood vessels, and stimulates Na+ excretion in urine.

182
Q

What effect does nitric oxide (NO) have on smooth muscle?

A

Nitric oxide (NO) activates soluble guanylyl cyclase, converting GTP to cyclic GMP, which relaxes arteriole smooth muscle.

183
Q

How does nitric oxide relate to the treatment of angina pectoris?

A

Nitroglycerin boosts NO production, raising cyclic GMP levels, relaxing coronary artery muscles, and treating angina pectoris.

184
Q

What is the primary action of receptor serine/threonine kinases?

A

Receptor serine/threonine kinases phosphorylate serine or threonine residues in proteins.

185
Q

What triggers the initiation of phosphorylation in receptor serine/threonine kinases?

A

Phosphorylation is initiated on serine or threonine residues in complementary receptors following ligand binding.

186
Q

What role does TGF-β play in the body?

A

TGF-β plays a role in embryogenesis and wound healing.

187
Q

What is the consequence of the phosphorylation of the type I subunit in TGF-β receptors?

A

Activates different downstream substrates and regulatory proteins, leading to the transcription of target genes.

188
Q

What cellular processes are influenced by the activation of TGF-β downstream substrates and regulatory proteins?

A

Differentiation, chemotaxis, proliferation, and activation of many immune cells.

189
Q

_____ are high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones.

A

Receptor tyrosine kinases (RTKs)

190
Q

What happens upon ligand binding to nerve growth factor receptors?

A

Dimerization and activation of tyrosine kinase activity.

191
Q

Describe the composition of insulin receptors and the process of their activation.

A

Composed of 2 alpha and 2 beta subunits, activation occurs when insulin binds to the alpha subunits, causing a conformational change,

192
Q

What action do activated insulin receptors perform after ligand binding?

A

Phosphorylates cytoplasmic proteins to initiate its cellular effects.

193
Q

What is the general action of receptor tyrosine kinases?

A

Phosphorylate tyrosine residues.

194
Q

Describe one of the pathways activated by RTK phosphorylation and its cellular outcome.

A

One of the pathways involves the activation of the small G-protein Ras,
leading to MAP kinase activation and the production of transcription
factors in the nucleus, which alters gene expression.

195
Q

Which class of catalytic receptors have no intrinsic kinase activity but associate with proteins that have tyrosine kinase activity?

A

Tyrosine Kinase Associated Receptors

196
Q

Which families of proteins do Tyrosine Kinase Associated Receptors typically associate with?

A

Tyrosine kinases of SRC family & JAK family

197
Q

What is the “ACTION” of Tyrosine Kinase Associated Receptors?

A

They interact with cytosolic tyrosine kinases (JAK).

198
Q

Tyrosine Kinase Associated Receptors bind several cytokines including __________-_ and ___________.

A

Interlukins-6
Erythropoietin

199
Q

Tyrosine Kinase Associated Receptors assemble into homodimers, heterodimers, or heterotrimers during ligand binding. How does this subunit assembly enhance the binding of tyrosine kinases?

A

It enhances the binding of tyrosine kinases by inducing kinase activity, which then leads to the phosphorylation of tyrosine residues on both the kinases and the receptor.

200
Q

How do Tyrosine Kinase Associated Receptors for cytokine and colony-stimulating factor receptors differ from other growth factor receptors?

A

They lack tyrosine kinase domains and have little or no cytoplasmic tail but are able to activate Janus tyrosine kinases (JAKs) in the cytoplasm to initiate tyrosine kinase activity.

201
Q

How does the JAK-STAT pathway work?

A

Tyrosine Kinase Associated Receptors activate Janus Tyrosine Kinases (JAKs) despite lacking tyrosine kinase domains → JAKs then phosphorylate STAT proteins, which form dimers and move to the nucleus to act as transcription factors.

202
Q

How is the family of nuclear receptors categorized?

A

It is divided into into 2 subfamilies based on structure & mechanism of action.

203
Q

What are the 2 subfamilies of nuclear receptors?

A
  1. Steroid hormone receptors
  2. Receptors that bind retinoic acid, thyroid hormones, and vitamin D
204
Q

What happens when ligands (lipid soluble) bind to nuclear receptors?

A

The ligand-receptor complex activates transcription factors that bind to DNA and regulate the expression of genes.

205
Q

Where can you locate nuclear receptors within the cell?

A

Cytoplasm
Nucleus

206
Q

Receptors located in the cytoplasm where they interact with chaperones such as heat shock proteins

A

Cytoplasmic receptors

207
Q

Binding of hormone to cytoplasmic receptors results in:

A

A conformational change that causes chaperones to dissociate from the receptor; this then uncovers a nuclear location motif that facilitates translocation of the hormone bound receptor complex to the nucleus

208
Q

Examples of cytoplasmic receptors

A

Glucocorticoid receptor
Mineralocorticoid receptor

209
Q

Nuclear receptors located primarily in the nucleus:

A

Estrogen receptor
Progesteron receptor

210
Q

Nuclear receptors located in the nucleus, bound to DNA:

A

Thyroid hormone receptor
Retinoic acid receptor
Vitamin D receptor

211
Q

When activated by hormon binding, nuclear receptors bind to:

A

Hormone response elements (HREs)

212
Q

What are hormone response elements (HREs)?

A

They are specific DNA sequences in the regulatory regions of the responsive genes

213
Q

Binding of ligand receptor to DNA causes a conformational change in DNA that:

A

Initiates transcription
Formation of mRNA

214
Q

How do nuclear receptors regulate gene expression?

A

By acting as transcriptional repressors
As an example, glucocorticoids suppress the transcription activator protein and nuclear factor which stimulate the expression of genes that cause inflammation. By this, glucocoticoids reduce inflammation

215
Q

(CLINICAL SCENARIO 1) A medical student volunteered in a Medical Mission in North Cotabato, The first patient he saw was a 35- year old man who had continuous, painless diarrhea in the past 24- hours. Stool was described as rice- watery and has a fishy odor.Patient was extremely weak and lethargic, and he complained of muscle cramps. He had sunken eyeballs, his oral mucosa was
dry, and he had poor skin turgor.
- Vital signs:
-Blood Pressure= 60/20 (hypotensive)
-Pulse Rate= 120/min
In this clinical scenario, what do you think happened to the
patient? What do you think is the etiology of the patient’s
symptoms?

A

The patient may have had an infection with a water- borne
infection called Cholera.

216
Q

What clinical symptoms are associated with cholera?

A

Cholera presents with severe, painless diarrhea (often described as
“rice water stools”), weakness, lethargy, muscle cramps, sunken
eyeballs, dry oral mucosa, and poor skin turgor.

217
Q

How does cholera toxin affect intestinal epithelial cells?

A

Cholera toxin is endocytosed by intestinal epithelial cells.
It acts on the G-alpha S subunit, leading to persistent activation of adenylyl cyclase.
This results in overproduction of cyclic AMP (cAMP) and continuous activation of
protein kinase A, leading to chloride loss, sodium loss, electrolyte imbalances,
and water loss.

218
Q

What is the mechanism of action of aspirin?

A

Aspirin inhibits cyclooxygenase in the arachidonic acid pathway, which has anti-clotting effects.

219
Q

How does Herceptin (used in breast cancer treatment) work?

A

Herceptin acts on the Receptor Tyrosine Kinase to decrease cancer growth in tumors with HER2 (Human Epidermal Growth Factor Receptor 2) overexpression.

220
Q

The patient in the clinical scenario 1 has a blood pressure of 60/20 mmHg and a pulse rate of 120/min. What is the most likely cause of his hypotension?

A

Dehydration due to electrolyte loss

221
Q

What is the role of cholera toxin in the pathogenesis of the disease?

A

It causes continuous activation of adenylyl cyclase, leading to excessive cAMP production.

222
Q

The patient in the clinical scenario 1 has significant electrolyte losses.
Which electrolyte is most likely to be lost in large amounts due to the activation of
CFTR channels by cholera toxin?

A

Chloride

223
Q

Aspirin inhibits the cyclo-oxygenase enzyme in the arachidonic acid pathway.
What is one clinical effect of this action?

A

decreased platelet aggregation

224
Q

How does Herceptin help in the treatment of HER2-positive breast cancer?

A

By blocking the HER2 receptor, reducing cancer cell growth

225
Q

What is the consequence of dysregulation of cellular signaling pathways involving phosphate timers?

A

Development of certain diseases

226
Q

Which of the following best explains the symptoms of muscle cramps in the patient with cholera?

A

Electrolyte depletion

227
Q

Given the clinical signs and symptoms, which laboratory test would confirm the diagnosis of cholera?

A

stool culture

228
Q

Why is it important to monitor platelet function in patients taking aspirin long-term?

A

Aspirin can cause excessive bleeding by inhibiting platelet aggregation.

Module 1B (7 decks)

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