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Module 102: Molecular cell biology > Cell Signalling > Flashcards

Cell Signalling Flashcards

1
Q

Why do cells need to communication with each other?

A
  • Allows adaptation to metabolism.
  • Allows communication with neighbouring cells.
  • Allows cells to respond to danger.
  • Allows cells to respond to growth.
  • Cause differentiation: especially in stem cells. Causes differentiation and proliferation.
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2
Q

Molecules used as signalling molecules.

A

Proteins: including insulin and interferon.

Peptides: including glucagon and Growth hormone.

Small chemicals: including steroids and dissolved gases like nitrous oxide.

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3
Q

The general pathway for intercellular signalling.

A
  1. A signalling molecule is released from a cell.
  2. The molecule is transported to a target cells
  3. The signalling molecule is detected by specific receptors on the plasma membrane of the target cell.
  4. This changes the cellular behaviour of the target cell.
  5. The signalling molecule or receptor is then somehow suppressed and made inactive.
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4
Q

The types of receptors used in signalling.

A

G protein receptors.

Enzyme linked receptors.

Ion channel linked receptors.

Receptors activated by ligands.

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5
Q

Inactivation of receptors

A

Receptors can be temporarily or permanently made unavailable.

This presents overreaction of a certain response. If this inactivation does not occur, can cause disease like chronic inflammation.

Receptors can be inactivated or made not functional.

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6
Q

The 5 different methods of intercellular signalling.

A

Endocrine- signalling molecules are hormones which travel over a long distance- metres

Paracrine- signalling molecules are released in small concentrations over a short distance.

Autocrine- Signalling molecules released activated the signalling cell.

Juxtacrine- Contact dependant signalling.

Neuronal- Signalling between neurones using synapses.

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7
Q

Endocrine signalling

Using examples

A

Cell communication over a long distance using hormones.

This requires all cells in the body to come into contact with the hormone, but do not all respond to it.

Examples: Glucagon and insulin released by the pancreas.
Cortisol released from the adrenal cortex.

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8
Q

Pancreas in endocrine signalling.

A

Contains endocrine tissue: Islet of Langerhans.

Alpha cells:

  • Secretes glucagon which acts on the liver cells
  • Causes them to release glucose to increase blood glucose levels.

Beta cells:

  • Secretes insulin which acts on adipocytes.
  • Causes the cells to store glucose in the form of adipose tissue.
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9
Q

Epidermal growth factor (EGF)

A

Local mediator signalling molecule.

Protein that stimulates the epidermal and other cells to proliferate.

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10
Q

Platelet-derived growth factor (PDGF)

A

Signalling molecule that can be released by platelets.

This protein stimulates many other specific cells to proliferate.

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11
Q

Histamine

A

Signalling molecule released from mast cells.

The molecule is derived from amino acid histidine and causes blood vessels to dilate and causes the walls to become leaky.

Important in inflammation.

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12
Q

Nerve growth factor (NGF)

A

Signalling molecule released by several innervated tissue.

It is a protein that promotes the survival of certain neurones and the growth of their axons.

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13
Q

Nitric oxide

A

Dissolved gas that can be used as a signalling molecule released by nerve cells and endothelial cells in blood vessels.

Causes relaxation of smooth muscles and regulates nerve-cell activity.

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14
Q

Nuclear receptors

A

Receptors located in the cytosol or on the nucleus.

Binding site for hydrophobic signalling molecules like steroid hormones.

When activated, it stimulates transcription regulators which change the synthesis of a certain protein.

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15
Q

Nitroglycerine

A

Drug used as a treatment for angina.

It is converted to nitric oxide which allow blood vessels to relax and dilate.

This increases blood flow to the heart and decreases the workload for the heart.

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16
Q

Components of intracellular pathways

A

RELAY:
The extracellular signal is relayed forward intracellularly to help spread the signal.

AMPLIFY:
Strengthens the signal received. Allows a small amount of extracellular molecules to give a large response.

INTEGRATE:
Signals from more than one signalling pathway is detected and combined to relay the same message forward.

DISTRIBUTION:
One molecule can distribute the signal to many effector proteins which give a complex/ multiple responses.

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17
Q

How are signalling pathways modulated?

A

Feedback regulation.

Positive feedback:
One of the molecules downstream acts on an earlier component in the same pathway to enhance response.

Negative feedback:
One of the molecules downstream acts as an inhibitor for one of the earlier components. This decreases the initial response.

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18
Q

Protein kinase

A

Enzyme that phosphorylates proteins in intracellular cell signalling.

Can only phosphorylate amino acids with OH group.

Serine/theronine kinase: phosphorylates proteins on serine or tyrosine .

Tyrosine kinase: phosphorylates proteins of tyrosine.

19
Q

Protein phosphatase

A

Enzyme that dephosphorylates proteins.

20
Q

GTP-binding proteins

A

A method of switching proteins in intracellular cell signalling.

When GDP is bound, protein is off. When GTP is bound, protein is on.

Proteins contain intrinsic GTP-hydrolysing activity- GTPase, this allows the break down of GTP to GDP.
Proteins can therefore shut themselves off.

21
Q

Signal transducer

A

A component that converts an extracellular ligand binding event into intracellular signals that alter the behaviour of a cell.

In cell signalling, the plasma membrane receptors are signal transducers.

22
Q

Ion-channel-coupled receptors

A

Also known as: ionotropic receptors.

Composed of ion channels permeable to a specific ion.
The permeability of the channel to the ion is changed by a signalling molecule.

23
Q

G-protein coupled receptors

A

Involves a G-protein (trimeric GTP-binding protein) mediating the interaction between:

  • Permanently bound plasma-membrane target protein
  • Activated receptor.

Signalling molecule binds to the 7 transmembrane domain receptor protein which causes a conformational change in the protein.

This activated receptor is a type of guanine nucleotide exchanging factor.
The activated receptor activates the alpha subunit of the G-protein, causing it to release GDP.

This allows GTP to bind to the alpha unit and activate the beta unit.

Alpha unit with GTP bound dissociates from the beta and gamma pair.

The different units go on to activate other proteins and enzymes in a relay signal.

G protein is deactivated when GTPase hydrolyses GTP back to GDP.

24
Q

Protein kinases

A

Phosphorylates proteins by adding a phosphate group to the OH of an amino acid.

Types:
Serine/threonine
Tyrosine

25
GTP-binding proteins
Molecular switch that controls activity of proteins in intracellular signalling. Protein is switched on when GTP is bound, and off when GDP is bound. The protein contains GTPase which hydrolyses GTP into GDP in order to make the protein inactive. G protein is a type of GTP-binding protein.
26
Regulatory proteins that control GTP-binding proteins.
GTPase activating proteins (GAPs) increase the rate of hydrolysis of GTP. This pushes the protein to become inactive. Guanine nucleotide exchange factor (GEFs) promote the release of bound GDP which allows GTP to bind.
27
G protein
Trimeric GTP-binding protein. Couples a receptor in cell signalling and causes cellular changes through intracellular signalling. Composed of three units: alpha, beta and gamma. Alpha unit is the binding site for GTP/GDP.
28
G proteins and the production of cAMP, using adrenaline
Adrenaline (primary messenger) binds to a G-protein coupled receptor. This causes a conformational change in the receptor which then activates the alpha unit of a coupled stimulatory G protein (Gs). The alpha unit binds to adenylyl cyclase to activate it. Adenylyl cyclase is an enzyme that forms cAMP from ATP. cAMP binds to protein kinase A which phosphorylates transcription regulators. When adrenaline is the primary messenger, this leads to the breakdown of glycogen into glucose, increasing blood glucose levels.
29
Cyclic AMP phosphodiesterase
Enzyme that breaks down cAMP to 5'-AMP.
30
Cyclic AMP dependant protein kinase (PKA)
Protein activated by cAMP. PKA phosphorylates specific serine or threonine.
31
G protein signals via phospholipids
G-protein coupled receptor activates its Gp (G protein) which causes the activation of the membrane bound enzyme: Phospholipase C-beta. Phospholipase C stimulates the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) by breaking down phosphatidylinositol 4,5-bisphosphate. IP3 diffuses to the sarcoplasmic reticulum and opens IP3 receptors, which is a calcium channel. Diacylglycerol and calcium ions activates protein kinase C (PKC) which phosphorylates several proteins.
32
How the cholera toxin affects G-proteins
Cholera toxin enters cells in the intestine and modifies the alpha unit of Gs protein. Binding to the alpha unit prevents it from hydrolysing the bound GTP, therefore the protein is always active and always produces adenylyl cyclase. This causes excessive flow of Cl- and water into the gut.
33
Calmodulin-dependant protein kinases (CaM-kinases)
Calmodulin is a protein that undergoes a conformational change when Ca2+ binds to it. CaM-kinase binds to calmodulin/calcium complex and this triggers the kinase to phosphorylate specific proteins
34
Enzyme-coupled receptors
Transmembrane protein that has a cytoplasmic domain that either acts as an enzyme or binds with other proteins to form an enzyme. The receptor spans the membrane once through its alpha helix. Binding of an extracellular signal causes two receptors to come together to form a dimer. The receptors activate their kinase domain and phosphorylate each other.
35
Receptor tyrosine kinase (RTKs)
A type of enzyme coupled receptor 1. Extracellular signalling molecule binds to the receptor. This triggers the receptor to form dimers. 2. The intracellular tails activate their kinases and phosphorylate specific tyrosines on each other. 3. This triggers the activation of other proteins by phosphorylation. RTKs activate Ras
36
Ras
A monomeric GTPase Only contains one unit that resembles the alpha unit of a trimeric GTPase Binding of Ras-GEF causes increased activation of Ras as GDP is exchanged for GTP. Ras-GAP deactivates Ras by stimulating hydrolysis of GTP.
37
Mitogen activated kinase (MAP protein)
The final kinase in the three-protein-kinase chain. Activation of a serine/threonine protein kinase leads to the phosphorylation of MAP. MAP phosphorylates effector proteins like transcription regulators
38
GPCRs activating K+ channels- in the heart
Muscarinic acetylcholine receptors Acetylcholine binds to the receptor which activates the G protein associated with it. The gamma unit binds to the potassium channel, causing it to open. This causes net flow of K+ out of the cell which leads to hyperpolarisation, preventing AP. This acts as pacemaker and slows heart rate down.
39
Voltage gated Nat+ ion channels
Change in voltage causes the ion channel to open. The alpha subunit of the channel contains 4 domains each with 6 transmembrane domains. Region 4 contains positive R groups which sense voltage change in membrane and move region 4 to open channel.
40
Pertussis toxin effect on G proteins
Causes whooping cough. Toxin binds to alpha unit and inhibits it from binding to adenylyl cyclase and associating with it's GPCR. Prolonged signal stimulates coughing.
41
Prolactin receptors
A type of RTK, receptor kinase receptor. Prolactin binds which forms a dimer and activates JAK 1 and 2 causing them to phosphorylate each other JAK 1 and 2 then phosphorylates the receptor and STAT 5. STAT 5 is activated and forms a dimer. STAT 5 dimer is a transcription factor 8
42
Receptor 'cross talk'
This is the integration of intracellular signalling. The activation of different receptors by different extracellular signalling causes the same cell response.
43
Calcineurin
Protein phosphatase that is activated by Ca2+.

Module 102: Molecular cell biology (8 decks)

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