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Miscellaneous > MCB Lecture 39 Cell to Cell communication > Flashcards

MCB Lecture 39 Cell to Cell communication Flashcards

0
Q

What are the types of ligand?

A 
Protein: growth factors
Steroids
Amino acids
Nucleotides
Hormones
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1
Q

Why is cell to cell communication important?

A

To relay signals from the external environment to the cell so it can modulate its activity

Growth
Development
Physiology

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2
Q

What are the types of receptor?

A
  1. Receptor tyrosine kinase
  2. GPCR
  3. Integrins
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3
Q

Where are receptors localised?

A

Membrane bound

Intracellular (nuclear or in the cytosol)

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4
Q

What are the 6 types of signalling?

A
  1. Contact dependent
  2. Paracrine
  3. Neuronal
  4. Endocrine
  5. Autocrine
  6. Gap junctions
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5
Q

Describe the two short distance types of signalling

A
  1. Contact dependent
    The cells must be very close
    The ligand is membrane bound
  2. Paracrine: ligands are released by cells and act on receptors on cells in close proximity to the cell
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6
Q

Describe the two types of very short distance signalling

A
  1. Autocrine
    Identical cells in a community all release these ligands which act on receptors on themselves
  2. Gap junctions
    Factors move through gap junctions to neighbouring cells
    Ca, cAMP
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7
Q

Describe the two types of long distance signalling

A
  1. Neuronal
    Ligands synthesised in cell body, travels down axon, secreted from synaptic vesicle.
    The ligand travels across the synaptic cleft to the receptors on the post-synaptic cell
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8
Q

What are the two types of receptors?

Describe the differences in the associated ligands

A

Membrane bound: protein ligands (hydrophilic)
Normally growth factors

Intracellular:
Lipid, steroid ligands
Hydrophobic

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9
Q

Describe the generic pathway for cell signalling (7)

A
  1. Primary Transduction: Ligand binds to receptor
  2. Relay: scaffold organises proteins involved in cascade
  3. Amplification: proteins produce a large number of factors
  4. Integration: a mediator receives signals from many pathways
  5. Spread: mediator produces diverging signals
  6. Effect: signal alters gene transcription

Anchor: cytoskeleton delivers certain elements

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10
Q

What is combinatorial signalling?

What are the generic outcomes of combinatorial signalling?

A

Many signals acting on a cell produce a concerted response

Survival
Divide
Differentiation
Death

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11
Q

Describe how one ligand may elicit different responses in different cell types

A

The receptor is different on the different cells

Heart cells: ACh binds to muscarinic receptor
Brings about the slowing of rate of contraction

Muscle cells: nAChR
Brings about muscle contraction

Salivary gland cells: muscarinic receptors
Brings about secretion of saliva

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12
Q

What are the two types of acetyl choline receptors?

A

Muscarinic

Nicotinic

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13
Q

Describe how steroid hormones signal

A

They travel in the blood with a chaperone, because this is an aqueous environment

Chaperone releases them very near to the cell membrane, which they pass through easily

Move not nucleus, bind to their receptor.

Receptor has multiple binding domains.
Gene transcription activated

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14
Q

Describe the features of a steroid receptor

What else does it require to be active?

A

Multiple binding domains

  1. Ligand binding domain
  2. DNA binding domain
  3. Transcription activating domain

Coactivation proteins

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15
Q

What are the two types of enzyme-linked cell surface receptors?

A

Receptor tyrosine kinases

Receptor Serine Threonine kinases

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16
Q

What types of ligands signal to cell surface receptors?

A

Protein: Growth Factors

Fibroblast GF, FGF
Epithelial GF, EGF

17
Q

Are growth factors monomers or dimers?

A

They can be monomers, dimers, multimers

18
Q

Describe how glucosaminoglycans can be involved in Growth factor signalling

A

These bind the growth factors, and present them to receptors

Or, they sequester them from receptors

19
Q

Describe the general features of Receptor Tyrosine Kinases

A
  1. Transmembrane domain
  2. Highly variable extracellular domains
  3. Variable intracellular domains
20
Q

Give an example of how membrane bound ligands act on receptors.

Give a specific example

What sort of processes use this type of signalling?

A

Ephrin ligand bound to the membrane
Eph receptor bound to membrane of a cell very near.

Important of development and cancer

21
Q

What is a dimerisation event?

A

When a ligand binds to a RTK, the two subunits come together and cross phosphorylate

22
Q

Describe the generic signal - transduction pathway in tyrosine kinase receptors

A
  1. Ligand binds
  2. Dimerisation
  3. Cross phosphorylation
  4. Transmission of signal
23
Q

What is Src?

A

It is a non receptor tyrosine kinase that has an SH2, SH3 and a tyrosine kinase domain

24
Q

What are Src Homology domains?

Differentiate between them

A

These are domains which are highly conserved in proteins that bind to phospho-tyrosines on RTKs

SH2: binds to phospho-tyrosine on RTK
SH3: binds to the GEF

25
Q

Where are Src Homology domains found?

A

Src

Grb2

26
Q

Describe the signalling stage of the Ras-MAPK pathway

A
  1. Ligand binds to RTK
  2. Dimerisation, cross phosphorylation
  3. Grb2 binds SH2 to RTK
  4. GEF (eg. Sos) binds to SH3 on Grb2
  5. GEF activates Ras
27
Q

In the Ras-MAPK pathway, which protein (with an SH2 domain) binds to a phospho-tyrosine of the RTK?

A

Grb2

28
Q

Which protein binds to Grb2 in the Ras-MAPK pathway?

Where does it bind?

A

A GEF, eg. Sos

29
Q

What is a GEF?

Give an example of one

A

Guanyl nucleotide exchange factor

Sos

30
Q

Describe how Ras is activated and deactivated

What are the other factors required to do this?

A

GEF removes GDP and puts on GTP

GAP activates hydrolysis of GTP

31
Q

What is the function of GAP? What does it stand for?

A

Hydrolysis of GTP

GTPase activating protein

32
Q

What are the general features of Ras?

Which two factors control its action?

A
  1. GTPase activity
  2. Activated by GEF
  3. Active for a very short amount of time due to GAP
  4. On / off switch
  5. A proto-oncogene
33
Q

What are the general players in a signal transduction pathway?

A

Ligand
Receptor
Intracellular proteins

34
Q

Describe how RTK and Ras are quickly deactivated. What does this mean for the pathway?

A

RTK: phosphatase a
Ras: GAP

This means that the pathway needs to amplify quickly

35
Q

How can the same steroid have different effects in different cells?

A

The coactivator proteins of the transcription factor may be different

36
Q

What type of receptor is an Eph receptor?

A

It is a receptor tyrosine kinase

37
Q

What sort of pathways do Eph receptors and ephrin function in?

A

Cell migration

Axon guidance

38
Q

A hyperactive Ras, that was resistant to GAP will lead to…

A

Cancer

Over proliferation of cells

39
Q

How is specificity of MAPK activation maintained?

A

MAPK has tyrosine and threonine residues –> only Mek can phosphorylate both of these

40
Q

What are the difference between Tyr-Pi and Ser-Pi and Thr-Pi?

A

Serine and threonine phosphate are longer lived, ie they are acted upon less by phosphatases

Thus the MAPK cascade has a chance to build up

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