Signalling

Question 1

why is signalling important in medicine

Answer 1

often conditions are caused by an error in signalling - if we understand signalling, we can improve prognosis and treatment

Question 2

examples of signals

Answer 2

O2
temperature
hormones/ growth factors
glucose levels
pathogens

Question 3

Homeostasis

Answer 3

e.g. control of blood glucose levels
- too high = insulin released
- too low = glucagon released

Question 4

diabetes

Answer 4

result of improper signalling
- type 1 is a lack of sufficient insulin production
- type 2 is reduced responsiveness to insulin target cell

Question 5

two main methods of transduction

Answer 5

enzyme cascades
second messengers

Question 6

enzyme cascades

Answer 6

often activated in response to growth factor RTK activation
relay proteins Grb/Sos activate Ras -> activated MAP kinase cascade
- multiple different MAPK cascades for different receptors

Question 7

second messenger definition

Answer 7

a small molecule produced in large amounts inside a cell after receptor activation e.g. cAMP

Question 8

second messenger example: adrenaline

Answer 8

GCPR -> adenyl cyclase -> cAMP -> PKA activation -> effector proteins phosphorylated

Question 9

phospholipase C activation

Answer 9

DAg -> IP3 -> Ca2+ -> Ca- -> CaMKs (enzymes)

Question 10

possible responses

Answer 10

-gene expression
-protein activity (e.g. phosphorylation alters metabolic enzyme activity)
-protein binding
-protein localisation (e.g. transcription factor activated by moving from cytosol to nucleus)

Question 11

types of signals

Answer 11

physical - pressure, temperature
electrical - nerve cells
bio(chemical) - hormones
growth factors
hormones

Question 12

types of hormones

Answer 12

1- amino acid derivatives (Adrenaline)
2- steroid hormones (testosterone, cortisol)
3- eicosanoids (prostaglandins)

endocrine - long distance, via blood
paracrine - short distance, by diffusion
juxtracrine - neighbouring cell, via cell-cell contact
autocrine - same cell

Question 13

intracellular receptors

Answer 13

testosterone
hydrophobic signal molecules can diffuse through plasma membrane into cell or NO
bind directly to intracellular receptor proteins
hormone-receptor complex acts as a transcription factor
complex binds to DNA and alters gene expression

Question 14

CSRs

Answer 14

water-soluble/ hydrophilic signal molecules must use a CSR protein (adrenaline/ insulin)
hormone ligand binds to CSR and alters its shape, altering function -> cellular response

Question 15

types of CSRs

Answer 15

ion-channel-linked (glutamate neurotransmitter)
g-protein-linked (adrenaline, serotonin)
enzyme-linked (key subtype = Receptor Tyrosine Kinases (RTK); growth factors)

Question 16

ion-channel linked

Answer 16

ion flow into cell changes electrical properties of a cell
- e.g. nerve impulse transmission

Question 17

G-protein-linked

Answer 17

activated G-protein activated enzyme that passes on signal into cell
- large heterotrimeric G-proteins are not the same a small monomeric g-protein like Ras
signal molecule activated G-protein -> activated an enzyme
-> changes in the cell
G-protein-coupled-receptors (GPCR)

Question 18

enzyme-linked

Answer 18

signal molecule binds to two parts of enzyme -> creates the active site needed for the changes in the cell
- may be dimeric, binding to the two different molecules to create the catalytic activity in the cytoplasmic domain
- may cause conformational change
protein phosphatase = removes a phosphate group form a target protein
protein kinase = an enzyme that uses ATP to phosphorylate a target protein reversibly

Question 19

process of enzyme linked receptors

Answer 19

ligand binding -> receptor dimerization and activation -> autophosphorylation -> docking sites -> relay proteins recruited, transmit signal further into cell

Question 20

specificity of signalling

Answer 20

a cell’s response to a given signal depends on the types and levels of receptors, transducers and effectors are expressed in that cell type;
- genes same; expression differs
-this means that same hormone can have different effects in different tissues

Question 21

in vivo specificity

Answer 21

specific GPCRs use only a specific subset of G-protein types, which couple to only a specific subset of target proteins

Question 22

pharmacology with signalling

Answer 22

GF/ RTK pathways often overactive in cancer cells
- activation mutation or overexpression, of RTK or other pathway proteins
treatment = inactivation antibodies or small molecule kinase inhibitors