Cell Signaling Flashcards

1
Q

What are the 3 stages of cell signaling?

A

1. Reception
(receptor binds to ligands)

2. Transduction
(receptor protein changes and activates intracellular molecs aka 2nd messengers)

3. Cell Response

(cell responds to signal)

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2
Q

What is another name for G-protein coupled receptors?

A

7-pass transmembrane receptors

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3
Q

What do the alpha and gamma subunits do for GPCRs?

A

anchored to cell membrane and keep G-protein next to the receptor

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4
Q

What does a GPCR bind to when it’s inactive?

A

GDP

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5
Q

What happens to GPCR when its alpha subunit is bound to GTP?

A

alpha subunit seperates from beta and gamma subunits and alpha subunit is then free to interact with other proteins

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6
Q
A

Gq

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7
Q
  • Bound to adenylate cyclase but inhibits it, causing (-) feedback to Gs

**negative feedback is important with helping to inactivate cells

A

Gi

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8
Q
  • stimulates adenylate cyclase
  • Activated adenylate cyclase takes ATP and removes 2 phosphate molecs transforming it into cAMP
  • regulated subunit then dissociates from catalytic subunit
A

Gs

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9
Q

Single pass transmembrane proteins (meaning they have 1 transmembrane segment and intracellular end has intrinsic cellular activity)

A

Enzyme coupled receptor

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10
Q

What are the 2 parts of enzyme coupled receptors?

A
  1. Receptor
  2. Enzyme (protein kinase that phosphorylates receptor)
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11
Q

What are the 3 main types of ECRs?

A
  1. Tyrosine Kinase associated Receptor
  2. Receptor Tyrosine Kinase
  3. Receptor Ser/Thr Kinase
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12
Q
  • most common enzyme coupled receptor
  • has many subfams
  • can’t phosphorylate its own Tyr side chains
A

receptor tyrosine kinases

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13
Q
  • Works similarly to receptor Tyr Kinase
  • no intrinsic enzyme activity
  • receptor binds to ligand
  • Cytoplasmic Tyr Kin
  • Phosphorylates target proteins to relay signal
A

Tyr Kinase associated Receptor

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14
Q
A
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15
Q

Type ii - Ser/Thr kinase domains receptor phosphorylates and activates type i receptor which recruits and phosphorylates various target proteins to relay signal

A

Receptor Ser/Thr Kinase

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16
Q
A

Ion Channel Receptor

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17
Q

Activates a receptor that has access to 2 signal pathways. However, the biased ligand only activates 1 of the pathways

A

Biased ligands

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18
Q

Discuss the concept of FM (Frequency Modulated) hormone signaling and give an example.

A

Fidelity of FM radio is better than that of an AM radio. It is the frequency (number of spikes/sec) is the determinant (critical variable)

Low freq pulses on the left cause little change in calmodulin kinase activity compared with high freq changes on the right.

19
Q

Describe the role of macromolecular complexes in cell signaling with examples.

A

A-kinase Anchor Protein (AKAP)

Pyruvate dehydrogenase complex

Causes many biochemical events that leads to cell activation and effector responses

20
Q

Describe the importance of location in cell signaling and mechanisms involved in creating signaling domains / “signalosomes”.

A

This makes sure that signaling molecules/ enzymes encounter the right substrates at the right place at the right time

Improves efficiency by boosting local concentration of signaling and their targets

Ex: B1AR (distributed across entire cell surface, including T tubules) and B2AR (distributed only on T tubles in muscle cells and are part of the mech involving calcium) are differentially distributed across the membrane instead of just in the T tubules. This leads to cardiotoxicity/ programmed cell death

In a failing heart, B2AR location is disrupted and instead distributed

21
Q

Give examples of the importance of membrane fluidity in cell signaling.

A

If you drink a lot of alcohol (like an alcoholic) alcohol is inserted into the membrane. This increases membrane fluidity. As a result, this messes with the way cells interact and signal each other. Target cells are able to recognize this and changes membrane lipid composition to adjust the problem.

Cholesterol (blood lipid): affects ability of proteins embedded in the membrane (including receptors) to change their configuration (think denaturing protein structure). Like trimeric G protein activation. Cholesterol affects ability to reconfigure properly

Woodchucks: In order to get through hibernation, cold body temp require them to adjust their membrane lipids to be made seasonally to maintain fluidity. This can be done by increasing unsaturated FA chain or increase proportion of short chain FA due to reduced Vander Waals interactions

22
Q

Define the role of hormone surface receptor regulation in determining hormone sensitivity and responsiveness.

A

****Not all receptors available have to be bound in order to achieve maximal response

LDL receptor story:

LDL travels in blood and bound to LDL receptors on surface of the protein. Once bound, the whole complex is internalized. Delivering LDL to the cell and removing LDL from the surface. When the cell has all the intracellular LDL, it doesn’t take much up anymore due to reduced number of plasma membrane receptors. This is bc LDL has become relocated in the interior so there aren’t anymore on the surface. But when cell needs LDL, more appears on the surface (negative feedback)

23
Q

Define homologous receptor regulation, its physiologic significance and the mechanisms proposed to explain the process.

A

Hormones are regulating their own receptor (Ex: epinephrine or insulin)

Internalization

**there is a reciprocol relationship between hormone concentration and receptor function

24
Q

Define heterologous receptor regulation.

A
  • 1 hormone is regulating receptors for a different hormone
  • Menstrual cycle
25
Q

Define the enzymes involved in synthesis and degradation of cyclic-AMP.

A

Synthesis: adenylyl cyclase

Degradation: cyclic AMP phosphodiesterase

26
Q

Which of the following statements best describes receptor tyrosine kinases (RTKs)? RTKs:

A

autophosphorylate themselves.

27
Q

Phosphorylation of tyrosine amino acid residues of the surface receptor protein in the signal pathway for growth factors such as epidermal growth factor or insulin (1)_______ ; while phosphorylation of serine or threonine amino acids on that receptor (2) _______ the signal pathway.

A

Activates, Inactivates

28
Q

Define the enzymes involved in synthesis and degradation of cyclic-AMP

A

Synthesis: adenylyl cyclase

Degradation: cyclic AMP phosphodiesterase

29
Q

What is involved in the cAMP signaling cascade for cell differentiation, proliferation, etc?

A
  1. GPCR is activated by change when the appropriate signal is bound (Heterotrimeric which is made of alpha, beta, and gamma subunits), found at cell surface and is needed for cell surface hormone signaling pathways)
  2. Gs complex is now activated
  3. cAMP is then activated by Gs
  4. cAMP causes inhibitory unit to fall off of PKA so PKA can phosphorylate and be active
30
Q

What does PKA phosphorylate to (most often) turn off receptors?

A

PKA phosphorylates either serine or threonine 99% (1% is Tyrosine)

31
Q

What are the 3 types of signaling molec categories?

A
  1. Hydrophilic - e..g amines (epinephrine, adrenaline in ANS), peptides (Signaling molecs in brain), proteins (insulin)
  2. Hydrophobic - Steroids, Thyroid hormones
  3. Gases
32
Q

How do surface acting hormones do their signaling?

A
  1. There needs to be a specific external signal for cell to respond to (HORMONE)

(in radio: specific radio waves)

  1. Cell recognizes signal via a receptor that allows the signaling molec to bind

(in radio, this is what recognizes the sound waves)

  1. The bound hormone now must be translated into a recognizable signal via transducer (G-protein)
  2. Amplification (Adenylate Cyclase) since now we understand the signal so, we wanna make it big enough to have an actual effect in the body. This is accomplished by 2nd messenger (e.g. cAMP)
33
Q

What does it look like when the receptor itself is an ion channel?

A
  • Ligand/hormone binds directly to an ion channel and binding causes the channel to either open or close (e.g. Ach)
  • Think about Ach, excitable membranes, nerve signal transmission at synapses between nerves; and between nerves and skeletal muscles (causing muscle contraction)
34
Q

What are the 4 types of surface receptor mechanisms?

A
  1. receptor itself is an ion channel
  2. receptor itself can be an enzyme
  3. GPCR
  4. Extracellular matrix through connection w the cytoskeleton
35
Q

What is cAMP’s key action?

A

Activate PKA by causing the inhibitory regulatory subunit to fall off

36
Q

What’s Ach’s job?

A
  • major neurotransmitter in the Central and Autonomic Nervous Systems (CNS / ANS)
  • major role is to open sodium channels in the membrane, the end result of which is membrane depolarization. This causes events such as transmission of electrical signals at synapses
37
Q

What are the 3 parts of the G-protein cAMP signaling cascade?

A
  1. receptor (GPRCR)
  2. G-protein (trimeric w alpha, beta, and gamma subunit) in this case, Gs to stimulate adenylyl cyclase
  3. embedded in the membrane is adenylyl cyclase (key enzyme)
38
Q

What does the trimeric G-protein cycle look like?

A
39
Q

What does Gs do?

A

activates adenylyl cyclase; activates Ca2+ channels

40
Q

What does Gi do?

A

inhibits adenylyl cyclase

41
Q

What does Gq do?

A

activates phospholipase C-beta

42
Q

How does Tyr phosphorylation have a special place in regulatary pathways?

A

Special place involved w normal cell proliferation and growth and cancer

43
Q

What is CREB

A

cAMP response element binding protein

44
Q

What does the CREB steps look like for creating new machinery?

A

Note that the cell is creating new or destroying current signal machinery! It is NOT altering the activity of existing machinery