Cell Signaling (L22) Flashcards

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1
Q

What is signal transduction?

A

The conversion between signaling molecules.

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2
Q

What are the 5 types of cell signaling?

A
  1. Endocrine signaling
  2. Paracrine signaling
  3. Autocrine signaling
  4. Synaptic signaling
  5. Contact-Dependent signaling
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3
Q

What are the two types of receptors that extracellular signaling molecules can bind to?

A
  1. Cell-surface receptors
  2. Intracellular receptors
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4
Q

What do cell-surface receptors bind?

A

Large hydrophobic signals that can’t cross the phospholipid membrane.

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5
Q

What do intracellular receptors bind? Where are they located?

A

They bind small, hydrophobic signals that can pass through the bilayer (ex: steroid hormones).

They are located in the cytosol and nucleus.

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6
Q

Signals tell the cell to do these four things:

A
  1. Grow/divide
  2. Differentiate
  3. Survive
  4. Die
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7
Q

What makes a response time to a signal molecule slow?

A

Whether or not it involves altered protein synthesis.

Fast = altered protein function
Slow = altered protein synthesis

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8
Q

Two types of molecular switches:

A
  1. Phosphorylation trigger
  2. GTP-Binding proteins
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9
Q

How does the phosphorylation trigger activate?

A

Protein kinase - adds phosphate group, activates

Protein Phosphate - dephosphorylates, inactivates

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10
Q

How do switch proteins controlled by phosphorylation function?

A

Through phosphorylation cascades

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11
Q

In which state is a GTP-Binding protein active? How do they deactivate?

A

When it is bound to GTP. Deactivates by hydrolyzing GTP.

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12
Q

What are the three classes of cell-surface receptors?

A
  1. Ion-channel-coupled receptors
  2. G-protein-coupled receptors
  3. Enzyme-coupled receptors
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13
Q

Ion-channel-coupled receptors

A

Transduce chemical signals into electrical ones

Allows rapid transmission of signals across synapses

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14
Q

How do ion-channel-coupled receptors work?

A

Neurotransmitter binds to receptor, altering its conformation to open a channel in PM.

Electrochemical gradients drive ion movement in/out of cell, changing membrane potential.

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15
Q

G-Protein-Coupled Receptors

A

Structure: single polypeptide chain that threads across membrane 7x

Stimulation activates G-protein subunits on cytosolic side of PM.

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16
Q

G-proteins

A

Complex of 3 proteins: alpha subunit is bound to GDP.

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17
Q

How does the G-protein conformational change occur?

A

When signal molecule binds to GPCR, alpha subunit decreases affinity for GDP and binds GTP.

The activated alpha complex departs, and the two subunits (alpha and beta-gamma) interact directly with target proteins in the PM.

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18
Q

How do G-proteins “turn off?”

A

When alpha-GTP hydrolyzes to alpha-GDP, it returns to its original conformation

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19
Q

What is glutamate? Which receptor will it bind to?

A

An excitatory neurotransmitter.

It will bind to an ICCR

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20
Q

What will glutamate do?

A

Binds to ICCR

Allows Na+ to flow into cell, resulting in action potential

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21
Q

Too much glutamate results in:

A

Linked to ALS and schizophrenia

22
Q

What type of receptor responds to light?

A

Specialized GCPRs

23
Q

What is the GPCR signal amplification mechanism?

A

Release of secondary messengers when G-proteins activate membrane-bound enzymes that produce them

24
Q

What is an example of a secondary messanger?

A

Cyclic AMP, produced by adenylyl cyclase

25
Q

What is cAMP made from?

A

ATP

26
Q

What is the cAMP pathway?

A
  1. Activated alpha subunit switches on adenylyl cyclase
  2. cAMP synthesis from ATP increases
  3. cAMP phosphodiesterase converst cAMP to normal AMP
  4. Activator enzyme PKA catalyzes the activation (phosphorylation) of serines and threonines (including some transcription genes)
27
Q

How does cholera work?

A

Acts through GPCRs

Modifies G protein subunit so it can’t hydrolyze GTP

Never turns off!

28
Q

How do enzyme-couple receptors commonly act?

A

As local mediators

29
Q

What is the biggest class of enzyme-couple receptors?

A

RTKs (receptor tyrosine kinases)

30
Q

How do RTKs work?

A

Signal binding causes receptor dimerization and autophosphorylation

31
Q

What is Ras?

A

A small, GTP-binding protein that is attached to the cytosolic side of the plasma membrane

32
Q

What activates Ras?

A

RTKs

33
Q

What is the active conformation of Ras?

A

Ras-GTP. Transmits signaling into cytoplasm by triggering a phosphorylation cascade.

34
Q

What do Ras-GEF and Ras-GAP do?

A

GEF: encourages Ras to trade GDP for GTP
GAP: promotes hydrolysis of GTP to GDP

35
Q

Outline the MAP kinase pathway

A
  1. Ras triggers series of phosphorylation
  2. Phosphorylation of each kinase activates it.
  3. After 3 rounds of amplification, effector proteins are phosphorylated by MAP kinase
  4. These effector proteins can change gene expression and protein activity
36
Q

What mutation does cancerous Ras have?

A

Inability to hydrolyze GTP, leads to uncontrolled cell growth

37
Q

Cells do this when they don’t receive signals

A

Die

38
Q

Hanahan + Weinberg hallmarks of cancer

A
  1. Evading apoptosis
  2. Self-sufficiency in growth signals
  3. Insensitivity to antigrowth signals
  4. Tissue evasion and metastasis
  5. Limitless reproductive potential
  6. Sustained angiogenesis
39
Q

Signaling strategies in plants

A

Have few GPCRs, RTKs, and do not use cAMP.

Signaling causes relief of transcriptional inhibition.

40
Q

What does ethylene signal a plant to do?

A

Ripen fruit

41
Q

Which receptor pathways tend to overlap?

A

GPCRs and RTKs

42
Q

Describe endocrine signaling

A

-Long range
-Systemic via hormones
-Transport by bloodstream/sap

43
Q

Describe paracrine signaling

A

-Short/long range (across tissue)
-Local mediators
-Signals released into extracellular fluid, move by diffusion to act locally (cell to cell)

44
Q

What is autocrine signaling?

A

A type of paracrine where the cell receives its own signals

45
Q

Describe synaptic signaling

A

-Fast
-Electrical signaling (action potential) results in release of neurotransmitters stored in vesicles at the synapses

46
Q

Describe contact-dependent signaling

A

-Cell surface bound signal molecule binds to receptor protein on an adjacent cell
-Physical contact, signal never leaves signaling cell

47
Q

What is an example of contact-dependent signaling?

A

Delta/Notch signaling

Delta (signaling cell) binds to receptor Notch on another, causing Notch to cleave into 2. The cytosolic subunit travels to nucleus and acts as a transcription regulator.

48
Q

Describe the general extracellular receptor pathway:

A
  1. Relay
  2. Amplification
  3. Integration of signals
  4. Distribution
  5. Feedback
49
Q

What is positive feedback?

A

Downstream element acts on upstream component to enhance response to initial signal

Switch: all/none

50
Q

What is negative feedback?

A

Downstream component inhibits upstream component to diminish signal.

Oscillation: inhibitory elements rise and fall