Intracellular Signalling Flashcards Preview

102 > Intracellular Signalling > Flashcards

Flashcards in Intracellular Signalling Deck (20)
Loading flashcards...
1
Q

What are the examples of intracellular signals? (2)

A

Ions, gases proteins, second messengers

2
Q

How can Extracellular signals result in action in the cell?

A

The ligand binds to transmembrane receptors (which are normally hydrophobic), which undergoes conformational change to initiate intracellular singllaing.

For Action: Signal can be transducted or amplified via different intracellular signalling molecules to effector proteins for cell response.

3
Q

How are signal molecules interpreted? (3)

A
  1. Post-translational Modification e.g Phosphorylation
  2. G protein binding to GDP or GTP.
  3. Second messengers/activators such as Ca2+ and cAMP.
4
Q

Describe Protein Phosphorylation. What enzymes are involved? (3)

A
  1. Phosphorylation involves addition of phosphate group to a protein.
  2. KINASE enzyme phosphorylates proteins and PHOSPHATASE dephosphorylates.
5
Q

What are the amino acids that can function as protein kinases? Why? (3)

A
  1. Serine
  2. Threonine
  3. Tyrosine.

They have free hydroxyl groups.

6
Q

What are the examples of Serine/Threonine Kinases? (4)

A
  1. Ca2+/calmodulin-dependent protein kinases (CaM kinases)
  2. Protein Kinase A (PKA)
  3. Protein Kinase C (PKC)
  4. Mitogen-activated protein kinases (MAPK)
7
Q

What are examples of Tyrosine Kinases? (2)

A
  1. Non receptor tyrosine Kinases e.g Src Family Kinases

2. Receptor tyrosine kinases (RTKs). e.g Epidermal growth factor receptor.

8
Q

GTP binding proteins? what are they and how do they work? (3)

A
  1. Small individual proteins involved in MOLECULAR switch mechanism.
  2. In GDP (Guanosine-5’-diphosphate (GDP)) bound state switch is off. Guanine exchange factors (GEFs) exchange GDP for GTP.
  3. In GTP (Guanosine-5’-triphosphate (GTP)
    ) bound state swtich is on. GTPase activating proteins (GAPs) help hydrolyse GTP back to GDP.
9
Q

Ras is a small GTPase, what happens when a mutation causes loss of Ras activity?

What condition is this associated with? (2)

A

The intracellular signalling stay activated because the molecular switch has not been turned off.

Associated with cancers. e.g Colorectal cancer.

10
Q

Describe a Voltage-gated ion channel (3)

A

It is made up of:
1. an Alpha subunits with 4 homologous domains which open in response to voltage.

  1. Each domain has 6 transmembrane region. The 4th domain has amino acids with positive Rgoups that sense voltage and move in response.
  2. 4 beta subunits which traffic the channel and regulate its kinetic properties.
11
Q

Describe a Ligand gated ion channel (3)

A
  1. These have a receptor and channel which transverse membrane.
  2. The channel opens in response to a ligand binding to receptor. The receptors are classified based on corresponding agonist.
12
Q

Describe Nicotinic acetylcholine receptor (3)

A
  1. Receptor is composed of 5 subunits (2 alpha, 1 beta, 1 gamma and 1 omega).
  2. The ‘M2’ region each subunit forms the channel.
  3. 2 acetylcholine bind to alpha subunits causing M2 helices to move and open channel.
13
Q

Calcium Signalling:
1. What type of events are regulated by Calcium

  1. How are Ca2+ ion movement regulated
  2. What type of channels do Ca2+ pass through?
A
  1. Skeletal muscle contraction, secretion, transcription factor activities.
  2. CaM kinase and Calcineurin phosphatase mediate Ca2+
  3. Ligand or voltage channels.
14
Q

Describe G-protein coupled receptors. How do they work? (5)

A
  1. They have 7 transmembrane domains but do not form pores.
  2. The G-protein has 3 subunits (1 alpha, 1 beta and 1 gamma), and floats freely intracellularly.
  3. When a signal binds to G-protein, the internal conformation changes, releasing GDP for alpha subunit.
  4. GTP replaces GDP. This activates the G protein, dissociating the Beta and gamma subunits which can each initiate further signalling.
  5. GTP is then hydrolysed back to GDP and subunits recombine to associate with another GPCR.
15
Q

How do GPCRs result in Protein Kinase A activation?

What Receptor is this important in? (3)

A
  1. GPCR -> Activated Gs alpha Protein -> Adenyl cyclase -> cAMP -> Protein Kinase A.
  2. Occurs in Beta 2 Adrenegic receptor to relax blood vessels in Skeletal muscle.
16
Q

How do GPCRs result in Phospholipase C activation?

How does Activating Phospholipase C result in activation of Protein Kinase C?

Where does this happen?
(4)

A

Occurs in M1 acetylcholine receptor for secretion.

  1. GPCR -> Activated G alpha Protein -> Phospholipase C.
  2. Phospholipase C -> Diacylglycerol;

Phospholipase C -> IP3-> Ca2+ from ER

  1. Diacylglycerol, Ca2+ from ER -> Protein Kinase C.
17
Q

How does GPCRs activate K+ ion channel?

What cell is this important? (4)

A

GPCR -> activated G alpha protein -> Beta and Gamma units attach to K+ channel, causing it to open -> K+ moves out of cell.

Important in Muscarinic M2 acetylcholine receptor in heart.

18
Q

How does Cholera interfere with GPCR and how does it cause damage to cells? (3)

A
  1. Cholera toxin inhibits GTPase activity in G alpha protein, leading uncontrolled stimulation of Adenyl cyclase.
  2. This causes water and Cl- to move out of cells lining intestine.
  3. Results in diarrhoea, dehydration and death.
19
Q

How does Whooping Cough interfere with GPCR and how does it cause damage to cells? (3)

A
  1. Whooping cough toxin inhibits GTPase activity in G alpha protein, leading uncontrolled stimulation of Adenyl cyclase.
  2. This prevents association of G protein with GCPR again.
  3. Prolonged signal results in constant coughing.
20
Q

How do receptor tyrosine kinases work? (3)

A

The ligand binds to the receptors:

  1. Receptors dimerise,
  2. Activating tyrosine kinase (through phosphorylation) in cytoplasmic region in response to signal.