LIGANDS and RECEPTORS

Question 1

Necessary for growth, migration, and differentiation of cells in the embryo and their tissue organisation.

Answer 1

Cell Communication

Question 2

How does Cellular Interactions proceed?

Answer 2

in Multiple Steps.
• 1. Production of signalling molecule.
• 2. Activation of the receptor.
• 3. Biochemical changes resulting in signal
transduction.
• 4. Signal sent to nucleus to affect gene expression (in many cases).

Question 3

Growth Factors/hormones classifaction

Autocrine

Paracrine

Endocrine

Synaptic

Juxtacrine

Answer 3

Autocrine- Same cell.
Paracrine- Close proximity.
Endocrine- At a distance.
Synaptic- Specific to nerve cells.
Juxtacrine- Direct contact.

Question 4

Combinatorial Signalling

Answer 4

Cells are exposed to many
ligands.

Cells must only respond to some of them.

Most cells must depend on a set of ligands to avoid programmed cell death.

Question 5

Ligands concentration and affinity

Answer 5

Ligands act at low concentration and they are recognised by their receptor with high affinity.

Question 6

Do ligands have only one response?

Answer 6

No,
The same ligand can induce different responses in different cells.
– The ligand bind to different receptors.
– The same receptor elicit different responses.

Question 7

Hydrophilic ligands

Answer 7

can’t cross through membrane) have transmembrane receptors

Question 8

Small liposoluble ligands

Answer 8

have to cross the membrane to reach an intracellular receptor.

Question 9

Receptors for Liposoluble Steroid Hormones

Answer 9

Inside the cell they bind to intracellular receptors and activate them

diffuse through cell membrane of target cells to act directly on gene expression

Question 10

Ligands That Bind to Cell Surface Receptors Are

Answer 10

Hydrophilic

cant not pass through membrane

Question 11

neurotransmitters

Answer 11

can not pass through membrane

small

Question 12

growth factors

Answer 12

most are small proteins
- 6-20 kDa in size

some are large
- 90 kDa

Question 13

3 Receptors for Hydrophilic Water Soluble ligands

Answer 13

Ion Channel Linked, G protein linked, Enzyme Linked

Question 14

Ion Channel Linked

Answer 14

Ligand open or close ion channel. Involved rapid synaptic signaling.

Question 15

G Protein Linked

Answer 15

se trimeric G protein as an intermediate to regulate activity of another membrane bound molecule.

Question 16

Enzyme Linked

Answer 16

Have enzymatic activity or are associated with enzymes when activated

Question 17

4 classes of enzyme coupled receptors

Answer 17

1. Receptor tyrosine kinases
2. Receptor tyrosine kinase associated receptors
3. Receptor serine/threonine kinases
4. Receptor tyrosine phosphatases

Question 18

3 domains in receptor tyrosine kinases:

Answer 18

1. Extracellular domain: large and glycosylated, binds to the growth factor.
2. Transmembrane domain: short and composed of hydrophobic amino acids.
3. Intracellular domain: contains the catalytic kinase domain.

Question 19

How Does the Binding of a Protein to the Extracellular Portion of a Receptor Tyrosine Kinase Regulate the Catalytic
Domain on the Other Side of the Protein?

Answer 19

1. Growth factor binding cause receptor tyrosine kinase dimerization.
2. Dimerization causes transphosphorylation of receptors.
3. Phosphotyrosines act as docking sites for SH2 containing proteins.
4. Some of those are themselves
   phosphorylated by the receptor.

Question 20

SH2 and SH3 Domains

Answer 20

Small Protein Modules

Their Function Is to Recognise Specific Amino Acids in Their
Target Proteins.

• SH2 and SH3 composed of approximately 100 and 50 aa respectively.
• SH2 and SH3 are Src homology regions 2 and 3.

They are usually shared by the various intracellular substrates of RTKs

Question 21

Substrates for Receptor Tyrosine Kinases Contain

Answer 21

SH2 Domains and Recognise Phosphotyrosine Residues

Those proteins do not bind to an inactive receptor.
• Some have enzymatic activity.
• Others only act to recruit other signaling molecules.

Question 22

The Phosphorylation Sites of a Receptor Will Determine

Answer 22

Which Substrates Bind

Question 23

What residues in a receptor are phosphorylated? What does it create?

Answer 23

specific tyrosine

They creates binding sites for specific substrates

Question 24

The specificity of the receptor to activate signaling pathways is

Answer 24

built into its primary sequence

Question 25

Ras

Answer 25

monomeric GTPase

Question 26

Ras Bound to GTP vs GDP state

Answer 26

– Bound to GTP: active.

– Bound to GDP: inactive.

Question 27

Sos

Answer 27

activates Ras by promoting GDP release

Question 28

GTP:GDP ratio

Answer 28

is 10:1 in cells

Question 29

GTPase activating proteins enhance

Answer 29

Ras GTPase activity.

Question 30

The Ras Proteins

Answer 30

Help Relay Signals From Receptor Tyrosine Kinases to the Nucleus to Help Stimulate Cell Proliferation or Differentiation

Question 31

protein phosphatase

Answer 31

is needed to remove it