Cell Signalling - Gray

Question 1

define 1st messenger

Answer 1

signal that goes between cells

Question 2

when does a signal molecule become a ligand?

Answer 2

when the signal binds the receptor it becomes a ligand

Question 3

what is the structural effect on a receptor when a ligand binds?

Answer 3

the receptor undergoes a conformational change

Question 4

describe the endocrine pathways

Answer 4

uses hormones as signalling molecules which are distributed by the bloodstream in animals. involved in long distance ‘communication’

Question 5

describe the paracrine pathways

Answer 5

GFs/controllers of development/histamines/neurotransmitters – diffuse out affecting surrounding cells, have short half-life. involved in short distance ‘communication’

Question 6

which endocrine molecule does the adrenal gland use? what type of molecule is it? what are it’s effects?

Answer 6

adrenaline
its a derivative of tyrosine (catecholamine hormone but you don’t need to know this)
Increases blood pressure, heart rate and metabolism

Question 7

which endocrine molecule does the pancreas use? what type of molecule is it? what are it’s effects?

Answer 7

insulin
insulin is a protein
it stimulates glucose uptake. protein and lipid synthesis in liver cells

Question 8

which endocrine molecule do the testes/ovaries use? what type of molecule is it? what are it’s effects?

Answer 8

testosterone
Steroid (derivative of cholesterol) (steroids often used for long-term maintenance) 
Induces and maintains secondary male/female sexual characteristics

Question 9

which cells does NO act upon? how does it travel around the body? is it paracrine or endocrine molecule? what are its effects?

Answer 9

acts upon cells lining blood vessels
travels as a dissolved gas
paracrine molecule
causes smooth muscles to relax

Question 10

which cells does GFs act upon? what type of molecule are they? are they paracrine or endocrine molecules? what are their effects?

Answer 10

acts upon various cells
it is a protein
paracrine molecule
stimulates cells to proliferate

Question 11

describe the effects of acetylcholine interacting with:

1) a heart muscle cells
2) a salivary gland cell
3) skeletal muscle cell

Answer 11

1) a heart muscle cells: decreased frequency of contraction
2) a salivary gland cell: secretion of saliva
3) skeletal muscle cell: contraction

Question 12

describe the signal transduction sequence

Answer 12

1) ligand (primary messenger) bind receptor
2) signal transduction via second messengers
3) cellular responses
4) changes in gene expression

Question 13

what type of molecule is a receptor?

Answer 13

protein

Question 14

define a signal transducer

Answer 14

a receptor protein - with the ability to detect small amounts of signal and convert them into another signal

Question 15

what kind of bonding occurs between a receptor and a ligand

Answer 15

non-covalent

Question 16

what type of receptor do hydrophobic/charged molecules bind to?

Answer 16

diffuse through the membrane and bind intracellular receptors

Question 17

what types of receptors do ligands bind to?

Answer 17

enzymes

G protein coupled receptors

Question 18

where do hydrophilic signals bind their receptors?

Answer 18

cell surface

Question 19

give an example of an intracellular receptor-ligand interaction with enzyme activity

Answer 19

NO gas binding to enzyme:
Activated enzyme catalyses synthesis of cyclic GMP (from GTP)
Relaxes smooth muscle surrounding blood vessels
Blood vessels expand, increasing blood flow
NO release by nerve terminals in penis causes local blood-vessel dilation (erection) – Viagra interferes with this by not breaking down cGMP

Question 20

give an example of a intracellular receptor-ligand interaction which regulate gene expression

Answer 20

steroid hormone receptors

• Steroid binds to site on receptor
• Activated receptor complex enters nucleus
• Binds to DNA to alter gene expression (eg secondary sexual characteristics)

Question 21

name the 3 major classes of cell-surface receptors

Answer 21

• Ligand gated ion channels
• Receptors with enzyme activity
• G-protein linked receptors

Question 22

describe a ligand gated ion channel. give an example of a neurotransmitter that uses one and describe how it works

Answer 22

Transmembrane protein forms a pore which ions can pass through
Opens/closes when signal binds to receptor protein
Acetylcholine:
- Has 2 binding sites
- When ligand bound, the pore opens (Na+ enters)
- Important in research – Alzheimer’s

Question 23

describe a receptor with enzyme activity and give an example of one

Answer 23

Has cytoplasmic domain in the cell
Must act as dimer – conformational change isn’t transmissible in a single molecule
Single pass transmembrane proteins
Most are protein kinases – add phosphate groups to proteins (adds -ve charge)

Question 24

describe how protein kinases work and the type of ligand used

Answer 24

Ligand binds to extracellular domain
Brings each half of the dimer (an intracellular kinase domain) closer together
Each monomer phosphorylates the other (phosphorylation occurs on specific amino acids)
This phosphorylation occurs again in multiple places
Kinases can activate other kinases
- Causes protein kinase cascades
Ligands are often peptide hormones eg insulin/GFs

Question 25

name 2 common protein kinase pathways

Answer 25

1) Ras pathway

2) PLC pathway

Question 26

describe the Ras GTPase switch, what is the effect of this pathway, what happens when Ras is mutated?

Answer 26

receptor activation causes Ras to bind GTP (turns it on)
Ras-GTP activates specific kinases which lead to cell proliferation
Ras GTPase activity hydrolyses GTP to GDP (turns it off)
Mutant Ras that can bind GTP but not hydrolyse it, found in many human tumours

Question 27

describe the PLC pathway

Answer 27

Phospholipase C is activated by a receptor (either receptor kinase or G-protein coupled)
PLC generates 2nd messenger IP¬3
- PLC cleaves PIP2 (a membrane phospholipid)
- Produces inositol trisphosphate (IP3) and diacylglycerol (DAG) – two 2nd messengers
- IP3 soluble and diffuses away from membrane
- IP3 causes release of Ca2+ from intracellular stores eg ER
- Ca2+ changes cell’s activity

Question 28

how many g-protein coupled receptor genes are there?

Answer 28

800

Question 29

what do g-protein coupled receptors do?

Answer 29

mediate diverse responses to hormones, neurotransmitters and local mediators (paracrine signals)

Question 30

why are G-protein coupled receptors called 7 pass receptors?

Answer 30

they pass through the membrane 7 times

Question 31

describe the activation of a g protein-coupled receptor

Answer 31

• Ligand binding activates receptor-associated G-protein by causing it to bind GTP (not GDP)
• G-protein relays the signal – it moves along surface of membrane and binds to effector enzyme
• Effector enzymes:
  i. Adenylate cyclase (catalyses the production of cAMP – cAMP is 2nd messenger)
  ii. PLC (catalyses the production of IP3)

Question 32

describe the mechanism of cAMP mediated responses

Answer 32

Ligand + receptor –> activated receptor –> activated G-protein –> activated adenylate cyclase –> increased [cAMP] –> activates (downstream) effectors