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Growth and Development > Cell signals and responses > Flashcards

Cell signals and responses Flashcards

1
Q

Types of cell communication

A

Remote signalling by secreted molecules
Contact signalling by membrane bound molecules (cell surface receptors on one cell bond to cell surface receptors of another cell)
Contact signalling via gap junctions

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2
Q

Endocrine signalling

A

Secreted

Hormone produced, enters bloodstream and is carried to target cell

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3
Q

Paracrine signalling

A

Secreted

Local chemical mediator released, acts on cells in immediate environment (e.g. cytokine)

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4
Q

Autocrine signalling

A

Secreted

On itself

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5
Q

Synaptic signalling

A

Secreted

Neurotransmitters released at synapses, diffuse to post-synaptic target cell

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6
Q

Order of cell signalling

A

Signal –> reception –> transduction –> response

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7
Q

Signal (outside)

A 
Growth factors
Hormones
ECM
Chemicals
Proteins
Sugars
Synaptic
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8
Q

Cell responses to signals

A 
Growth, cell division
Differentiation
Metabolism (faster or slower)
Apoptosis (tells cell to die)
Gene transcription
Secretion
Contract/ relax
Membrane charge (can generate a.p)
Migration (often towards signal e.g. chemokine)
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9
Q

How is transduction caused?

A

Signal –> cell surface receptor –> transduction

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10
Q

Examples of transduction

A

Amplification, phosphorylation cascades, secondary messengers

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11
Q

Intracellular receptors

A

Hydrophobic: can pass through plasma membrane
Transported into nucleus
Response: influence gene transcription
e.g. steroids, NO

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12
Q

Types of membrane receptors

A

G-protein linked
Tyrosine kinases
Enzyme linked
Ion channels

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13
Q

Monomeric (small) G-proteins

A

Ras
Family: H-Ras, K-Ras, N-Ras
Function controlled by GDP/ GTP cycle
Stimulates cascade of kinases (effectors)
Proliferation, differentiation, cell death

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14
Q

What does mutation do to Ras

A

Makes Ras insensitiveto GTPase activation proteins (active for longer i.e. on all the time)

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15
Q

Where are Ras mutations found

A

in ~30% of all tumours

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16
Q

G-protein coupled receptors

A

Integral trans-membrane proteins
Receptor occupation promotes interaction with G-protein
Promotes exchange of bound GDP for GTP
Activates G protein (α subunit) which leaves receptor
Initiates signalling through secondary messengers
-another way of switching on/ off protein

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17
Q

Why is cell signalling important?

A

For adaptation (e.g. to changes in environment), co-ordination and regulation

18
Q

What are endocrine hormones produced by?

A

Endocrine glands

19
Q

Do cytokines last long?

A

Have very short half-life, works for short time

20
Q

Two potential routes of signal to cell

A

Signal –> internal cell receptor

Signal –> cell surface receptor –> signal transduction

21
Q

Testosterone: hydrophilic or hydrophobic?

Describe pathway

A

Hydrophobic - can pass through cell membrane
Intracellular receptor
Binds to hormone-receptor coplex in cytoplasm, transported into nucleus, gene transcription altered, mRNA produced, new protein

22
Q

Example of post-translational modification. What does this do to protein

A

Phosphorylation (by kinase enzyme)
Phophorylation is like an on/off switch - big charge change
E.g. serine / threonine/ tyrosine

23
Q

How many times do G-protein coupled receptors cross membrane

A

7 times

24
Q

Are G-protein coupled receptors specific?

A

Yes, very. Won’t recognise other molecules

25
Q

LOOK AT WORD DOC

A

LOOK AT WORD DOC

26
Q

How many types of G-proteins

A

2

  • one that associates with receptors
  • one that doesn’t interact with receptors and floats around in cytoplasm (monomeric)
27
Q

Receptor tyrosine kinases

A

Dimerise upon ligand binding
Have intrinsic enzymatic activity
Puts phosphate from ATP on tyrosine (autophosphorylation)
Bind src homology-2 (SH-2) proteins
Initiates series of phosphrylation reactions

28
Q

What can complicated signal cascades do

A

Amplify signal

Lots of different levels to regulate process (fine tuning)

29
Q

Example of a transduction cascade

A

Mitogen activated protein (MAP) kinase system

30
Q

Enzyme linked receptors

A

Cytokine receptors

  • no intrinsic activity but associates with enzymes involved in phosphorylation - JAKs
  • rapid signal by shortcut system to nucleus by STATs
31
Q

Ion channels

A

Receptor is ion channel
Ligand (e.g. neurotransmitter) binds to and opens channel (some voltage gated)
Response: influx of Na+, change in membrane potential, a.p.

32
Q

Secondary messengers

A

Small molecules

Bind and activates other molecules

33
Q

Examples of secondary messengers

A

Cyclic adenosine monophosphate (cAMP)
Inositol triphosphate (IP3)
Ca2+
Diacylglycerol

34
Q

Control of signalling

A

Pathway leads to single response
Pathway branches leading to 2 responses
Cross-talk occurs between 2 patways (e.g. growth factor signalling)
Different receptor leads to diff response

35
Q

Example of control of signalling

A

Inhibition by protein phosphatases

36
Q

Example of specificity of signal

A 
Fibroblast growth factor receptor (FGFR) stimulation: 
-in fibroblasts - proliferation
-in neuronal cells - differentiation
Cellular compartmental isation e.g. STAT
Scaffold proteins
37
Q

Scaffold proteins

A

Acts like enzyme in cytoplasm - makes reaction much more likely to happen

38
Q

Difficulty with therapeutic targets for cancer

A

If you target cells that are growing, will also target normal cells as well

39
Q

Therapeutic targets

A

Cell signalling transmits mitogenic and survival signals
Over-expression in cancer - MAPK, PI3K
Constitutive expression - transformation
Activating mutations of G subunits and receptors
Specific inhibitors - PD184352 (MEK) reduce tumour growth by up to 80%
PTEN a tumour suppressor is a IP3 phosphatase

40
Q

What is the most important signalling molecules to target for tumours?

A

Epithelial growth factor receptors (most tumours are epithelial)

41
Q

Monomeric G-proteins and GDP/ GTP cycle

A

Inactive when bound to GDP

Phosphorylated (using ATP) to become bound to GTP –> active

Growth and Development (23 decks)

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