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BL2305 > Cell Signalling > Flashcards

Cell Signalling Flashcards

1
Q

What are the 8 general principles of cell signalling?

A

1 - Cell synthesizes signalling molecule
2 - This is released
3 - Transported to the target cell
4 - Activation of receptor
5 - Signal transduction pathway
6 - Short-term effect (function, metabolism, movement) or long-term effect (gene expression)
7+8 - Termination by inhibition or removal of signalling molecule

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2
Q

Describe the general pathway by which a signal produces a response in a cell after activating the receptor

A
  • Receptor activates the relay molecule
  • Transducer changes the form of the signal and produces second messengers which amplify the signal
  • Range of proteins activated which can bring signals from multiple pathways together (integrator)
  • Distributor can then enact changes on cell function
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3
Q

What 4 things make an effective signal?

A
  1. Specificity - defined cellular outcome
  2. Small - rapidly diffuse across membranes
  3. Made, mobilised & altered quickly
  4. Amplification
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4
Q

When does maximal physiological response occur in response to an extracellular signal?

A

When only a fraction of receptors are occupied by a ligand

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5
Q

What gives more opportunity for amplification?

A
  • Steps in the signal transduction process

- Also makes for a more dynamic, easily regulated system

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6
Q

Name 5 mechanisms for the termination of cell signalling

A
  1. Receptor sequestration
  2. Receptor down-regulation
  3. Receptor inactivation
  4. Inactivation of signalling protein
  5. Production of inhibitory protein
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7
Q

What is juxtacrine signalling?

A
  • Does not involve chemical messenger release
  • 2 neighbouring cells communicate via physical connections
  • Important for embryonic development
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8
Q

Describe notch signalling

A
  • Notch receptor on one cell targets receptors delta and serrate
  • Causes proteolysis of intracellular region of notch
  • Alters gene expression
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9
Q

What is autocrine signalling?

A
  • When a cell releasing a messenger also recieves said messenger
  • e.g Interleukin, Wnt, cancer cells
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10
Q

What is paracrine signalling?

A
  • When a chemical messenger diffuses across the extracellular matrix and activates neighbouring cells
  • Found in fibroblasts
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11
Q

What is endocrine signalling?

A

When secreting cell releases chemical into the blood stream which goes on to target distant cells

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12
Q

What are the 3 classes of hormones?

A
  1. Peptide/protein
  2. Steroids (neutral lipids derived from cholesterol)
  3. Amines derived from tyrosine
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13
Q

How are peptide proteins produced?

A

Produced by transcription/translation as prehormones which are then cleaved to form prohormones which are cleaved again to produce active hormones

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14
Q

Describe steroid hormones and give examples

A
  • Derived from 80% blood LDL cholesterol and 20% acetylcholine
  • e.g cortisol, testosterone, estradiol
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15
Q

Describe amine hormones

A
  • Derived from tyrosine

- Each has their own synthetic pathway and storage site

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16
Q

What are the 2 types of cell membrane receptors?

A

single membrane-spanning and multi membrane-spanning

17
Q

What is the major function of G coupled receptors?

A

The regulation of enzymes and proteins, allowing the cell to quickly respond to its environment

18
Q

What is the structure of tyrosine kinase receptors (RTKs)?

A
  • Single-pass with an intracellular tyrosine kinase

- Usually dimerise to function

19
Q

What do RTKs usually affect?

A

Predominantly bind to growth factors to influence transcription and cell proliferation/differentiation

20
Q

How do RTKs function?

A

Initiate phosphorylation via the tyrosine kinase domain for the recruitment of transducer proteins which then couple with amplifiers

21
Q

What is the structure of serine/threonine kinase linked receptors?

A
  • single pass

- serine/threonine intracellular domain

22
Q

How do serine/threonine kinase linked receptors function?

A
  • Serine/threonine acts as both a transducer and an amplifier
  • Recruits protein SMADS which then interacts with the nucleus in order to regulate gene expression
23
Q

Where can ion channels be found acting as receptors?

A

In neurons where they act as both transducers and amplifiers which can go on to have an effect on gene transcription or function

24
Q

What is the structure of G coupled receptors (GPCRs)?

A
  • 7 transmembrane regions with 3 extracellular and cytosolic loops
  • G protein bind to C3 and C4
  • Ligand binds to the extracellular side
25
Q

Describe the activation of a GPCR

A
  • Ligand bonds to the receptor causing G protein to be recruited
  • G protein allows GTP to bind to G alpha, causing the G protein to activate and for the alpha subunit to detatch from the beta and theta subunit
  • Subunit activates effector protein to transduce the message and bring about cellular change
26
Q

What are the 4 second messengers used by GPCRs?

A
  • Cyclic AMP
  • Cyclic GMP
  • Diacylglycerol
  • Inositol triphosphate
27
Q

How does the GPCR pathway activate protein kinase A (PKA)?

A
  • Activated G protein goes on to hydrolyse ATP to cyclic AMP
  • This then binds to PKA via a regulatory subunit which releases the catalytic subunit and activates the PKA
28
Q

What are the 4 ways in which a GPCR signal can be downregulated?

A
  1. Loss of receptor affinity for the ligand
  2. Inhibition of the receptor
  3. Downregulation of the second messenger
  4. Ubiquitination
29
Q

Describe how the GPCR may lose affinity for a ligand

A

Due to innate GTPase activity in the G alpha subunit, GTP is hydrolysed back to GDP causing the protein to become inactivated

30
Q

Describe the process feedback repression in PKA

A

PKA phosphorylates the receptor intracellular region by the recruitment of a large protein complex, causing inactivation of the receptor

31
Q

Describe how the downregulation of PKA can occur in the case of a second messenger

A
  • At resting state, PKA is bound to the membrane via mAKAP and PDE which degrades cyclic AMP
  • Increasing cAMP activity leads to PKA activation, which goes on to phosphorylate PDE which increases its activity
  • cAMP is quickly degraded and levels return to normal
32
Q

What is ubiquitination?

A

Where the addition of the small protein ubiquitin targets a protein to be broken up, or for the degradation of a receptor

BL2305 (17 decks)

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