Signalling

Question 1

Name some things cells may receive signals from

Answer 1

nutritional status, oxygen supply, temperature, pathogens, other cells, hormones, growth factors, pro-apoptotic factors

Question 2

Name some general responses cells may conduct when signalled

Answer 2

die, grow, divide, differenciate, migrate, change shape, change cell activity, produce new proteins, transcribe new genes, release hormones

Question 3

name 4 reasons/examples why cell signalling is important

Answer 3

coordinating development (fetal)
maintaining normal physiological functions (homeostasis)
diseases can be caused by abnormal signalling pathways (diabetes/cancer)
many drugs work by targetting signalling proteins (salbutamol)

Question 4

name 3 examples of signal types and examples for each

Answer 4

physical (pressure/temp)
electrical (nerve cells)
biochemical (hormones, growth factors, neurotransmitters)

Question 5

in what 2 ways can biochemical signals be classified?

Answer 5

chemical structure and range of action (distance)

Question 6

name 3 types of hormones and examples for each

Answer 6

animo-acid derivatives (adrenaline/peptide hormones)
steroid hormones, derived from cholesterol (testosterone)
eicosanoids, derived from lipids (prostaglandins)

Question 7

name the 4 classes of action range in signalling cells

Answer 7

long distance (endocrine - via blood)
nearby cells, by diffusion (paracrine)
neighbouring cell, via cell-cell contact (juxtacrine)
same cell (autocrine)

Question 8

explain the common 3 stages for all signals

Answer 8

detect sign stimulus

transduce the signal from site of detection to part of the cell that will respond

respond - must be coordinated with responses to other signals; and with responses of other cells (tissue/organ/body)

Question 9

what are intracellular receptors?

Answer 9

hydrophobic signal molecules that can diffuse through plasma membrane into cell
(steroid hormone, nitric oxide gas)

Question 10

how do steroid hormones signal?

Answer 10

binds to intracellular receptor proteins
hormone-receptor complex acts as a transcription factor
complex binds to DNA and alters gene expression

Question 11

how do hydrophilic molecules signal?

Answer 11

using a cell surface receptor protein
(insulin, adrenaline)

Question 12

name the 3 main types of cell surface receptors

Answer 12

ion channel linked
G-protein linked
enzyme linked

Question 13

describe the ion channel linked receptors

Answer 13

ion flow into cell changes electrical properties of cell, such as nerve impulse transmission
(e.g glutamate neurotransmitter)

Question 14

describe the G-protein linked cell surface receptors

Answer 14

activated g-protein activates enzyme that passes on the signal into the cell
very large heterotrimeric g-protein (3 subunits) or small monometric g-proteins
example - adrenaline, seratonin

Question 15

describe the enzyme linked cell surface receptor function

Answer 15

when signal binds to inactive receptor, the 2 receptor subunits combine, activating the enzyme that signals for a change in the cell
key subtype = receptor tyrosine kinases (RTK)
example - growth factors, insulin

Question 16

explain the 4 steps involved with RTK binding in enzyme linked receptors

Answer 16

singal dimer binds, kinase activity is stimulated, tyrosines are phosphorylated, intracellular proteins bind to phospho-tyrosine docking areas

Question 17

describe the process of signal amplication

Answer 17

one receptor molecule activates many relay molecules
different receptors use different transducers/amplifiers
done either by enzyme cascades or second messengers

Question 18

explain enzyme cascades (specifically MAPK) cascades

Answer 18

activated in response to growth factors (RTK activation)
produces relay proteins Grb/Sos which activates RAS (proto-oncogene)
RAS activates a ‘MAPK cascade’
cascade signal amplified

Question 19

explain second messengers

Answer 19

second messenger = small molecule produces in large amounts inside cell after receptor activation (cAMP)
second messenger coordinates cell response
(e.g adrenaline, GPCR -> cAMP -> PKS activation -> effector proteins phosphorylated)

Question 20

what are the general (not always) pairings for different amplication processes?

Answer 20

RTK = MAPK activation
GPCR = second messengers

Question 21

name 4 molecular level signal responses

Answer 21

gene expression
protein activity (phosphorylation)
protein binding (inhibitor/activator)
protein localisation (transcription factor activated by moving from cytosol to nucleus)

Question 22

explain the RTK pathways in cancer and treatment

Answer 22

RTK pathways often overactive in cancer, activating mutation or overexpression of RTK or other pathway proteins
treatment - inactivating antibodies or small molecule kinase inhibitors

Question 23

describe g protein coupled receptor activation (GPCR)

Answer 23

ligand binds to receptor, conf. change in cytoplasmic domain, conf. change allows g-proteins to bind and be activated by receptor, activated g-protein activates intracellular enzymes

Question 24

explain how the g-protein in GPCR works

Answer 24

GTP is similar to ATP (energy source)
GTP-bound: active
GDP-bound: inactive
activated g-protein activates downstream effector proteins
GAP/RGS proteins = ‘off switch’

Question 25

describe the effects of GPCR activation

Answer 25

can activate or inhibit intracellular enzymes or proteins directly
production of second messenger molecules

Question 26

explain how adrenaline is signalled by GPCRs to release glucose

Answer 26

in muscle/liver cell, adrenaline binds to GPCR, the activated g-alpha subunit will activate adenylyl cyclase molecule, activating cAMP which activated PKA
PKA activates glucose production by phosphorylase/kinase and inhibits glycogen storage by synthase

Question 27

explain multiple signalling pathways

Answer 27

one receptor can activate multiple signalling pathways, one signalling pathway can activate multiple different responses
(e.g EGF receptor for survival, proliferation and invasion)

Question 28

explain multiple signal integration through p53

Answer 28

the level of DNA damage (genotoxic stress) determines the signalling pathway
mild stress phosphorylates p53 at ser15 causing cell cycle arrest, severe stress phosphorylates p53 again at ser46 causing apoptosis

Question 29

how does adrenaline show specificity in signalling?

Answer 29

multiple pathways and functions:
- glucose release from skeletal muscle/liver
- increases HR/force
- blood vessel vasodilation/vasoconstriction
- bronchodilation

Question 30

how (molecularly) can adrenaline signal different specific responses?

Answer 30

can bind multiple GPCRs
multiple g-proteins each binding to GPCRs
multiple second messengers and protein kinase transducers (adenylyl cyclase subtypes)
multiple target proteins

Question 31

what factors influences a cells response to a given signal?

Answer 31

levels/types of receptor, transducers and effectors expressed in that cell type
genes same; expression differs, meaning the same hormone can have different effects in different tissues