TOPIC B: Cell signalling

Question 1

What does amplification mean

Answer 1

The number of affected molecules increasing geometrically due to a signalling cascade

Question 2

What are the 4 types of signalling + basic description

Answer 2

Contact dependent: cells in contact

Paracrine: released to neighbouring cells

Synaptic: Neurotransmitters at a synapse

Endocrine: hormones in bloodstream

Question 3

What are the 3 main classes of hormones + basic description

Answer 3

polypeptide/protein: Stored in secretory vesicles

amide hormones: developed from tyrosine like epinephrine and norepinephrine

steroid hormones: steroids similar in structure (cholesterol)

Question 4

What are the two main types of molecular switches + basic description

Answer 4

phosphorylation: kinase and phosphatase deactivate or activate

binding of GTP: exchange of GDP for GTP activates.

Question 5

What are the 2 broad types of receptors

Answer 5

Cell surface receptors

Intracellular receptors

Question 6

What are the 3 types of cell surface receptors

Answer 6

Ion channel coupled receptor

G protein coupled receptor

Enzyme coupled receptor

Question 7

What is the 1 type of intracellular receptor

Answer 7

Nucelar receptor

Question 8

What is an enzyme linked receptor

Answer 8

cell surface receptors linked intracellular enzymatic activity. Trigger a cascade.

Question 9

What are the 2 types of enzyme linked receptors studied in this course

Answer 9

receptor tyrosine kinases

tyrosine kinase associated receptors

Question 10

Describe activation of a receptor tyrosine kinase

Answer 10

when activated phosphorylate intracellular Tyr residues.

RTKs dimerise and then trans auto phosphorylation occurs.

Phosphorylation of tyrosine kinase domain acts as docking sites.

Question 11

What is a domain of a docking, adaptor or scaffold protein

Answer 11

Specific parts of protein which recognise certain regions on other proteins.

Question 12

Define a docking protein

Answer 12

Proteins embedded in the cell membrane, allows other proteins to dock to them

Question 13

Define an adaptor/scaffold protein

Answer 13

Protein that links/bridges one protein to another if they cannot bind to the receptor themselves. Allows further activation

Question 14

Explain the complex formed at the insulin receptor

Answer 14

insulin receptor is a receptor tyrosine kinase.

IRS1 binds when it is phosphorylated which allows other proteins to attach and become activated.

Question 15

Describe the MAPK pathway of a receptor tyrosine kinase

Answer 15

Insulin RTK activated causing binding of IRS1.

Grb2 binds to IRS1 allowing Ras-GEF (Sos) to bind and become activated.

Sos activates Ras protein by GDP/GTP exchange.

Ras activates Raf. Raf activates Mek which activates Erk by phosphorylation.

Erk phosphorylates proteins causing cell proliferation/growth/differentiation

Question 16

Describe the PI3K/Akt pathway of a receptor tyrosine kinase

Answer 16

Insulin RTK activated causing binding of IRS1.

PI3K binds activating it, causing it to phosphorylate docked inositol phospholipids.

This allows protein kinase 1 to dock and with protein kinase 2 phosphorylate and active Akt.

Akt causes multiple cell responses explained in different question

Question 17

What are the cell responses due to Akt activation

Answer 17

Phosphorylates Bad causing dissociation and activation of Bcl2 causing cell survival.

Protein synthesis, glycogenesis, gluconeogenesis, lipogenesis in liver

GLUT4 translocation and glycogenesis in muscle

GLUT4 translocation, lipogenesis in adipose

Question 18

What is a tyrosine kinase associated receptor

Answer 18

Enzyme linked receptor that couple to proteins that have Tyr kinase activity.

Question 19

Outline the activation of cytokine tyrosine kinase associated receptors

Answer 19

Cytokine binds causing dimerisation of receptors

JAK protein already attached to monomers is then activated causing them to phosphorylate each other and then the receptor.

This provides binding sight for STAT proteins which then form complex that travels into the nucleus and activates transcription.

Question 20

Describe a ligand gated ion channel

Answer 20

A cell surface receptor also called an ion channel coupled receptor.

open or close in response to a ligand

Question 21

Outline the physical characteristic of a GPCR

Answer 21

Cell surface receptor

7 transmembrane segments

extracellular N, intracellular C

Question 22

Define a G protein

Answer 22

guanine nucleotide binding proteins act as molecular switches by binding GTP to other proteins in the cell

Question 23

What enzymes activate and deactivate a G protein

Answer 23

Guanine nucleotide exchange factor (GEF): swaps GDP for GTP, activates

GTPase activating protein (GAP): hydrolyses GTP to GDP, deactivates

Question 24

Describe the trimeric complex of a G protein

Answer 24

alpha, beta and gamma units.

alpha unit works on its own as a GTPase

Beta and gamma work together

Question 25

Explain the activation of a G protein from a GPCR

Answer 25

GPCR activated by signalling molecule GPCR interacts with G protein G protein ejectes GDP for GTP, causing activation and releases beta gamma unit. unit activates other proteins delivering message throughout cell turned off when GTP is hydrolysed to GDP.

Question 26

Define an effector enzyme and a second messenger

Answer 26

Effector enzyme: More enzymes activated by a G protein or earlier protein in pathway Second messengers: affect later parts of pathway and are activated by effector enzymes

Question 27

Explain the activation of the inositol phoshpolipid GPCR pathway

Answer 27

GPCR activated causing activation of G protein beta gamma unit activates phospholipase C (effector enzyme in membrane) phospholipase C cleaves PIP2 into DAG and IP3 (second messengers) IP3 targets Ca channels of E.R causing Ca release Ca and DAG activate protein kinase C which activates cell response

Question 28

Explain the activation of the cAMP GPCR pathway.

Answer 28

GPCR and G protein activated unit activates adenyl cyclase to convert ATP to cAMP (second messenger) cAMP activates protein kinase A by binding to catalytic subunits, goes onto activate cell response

Question 29

Briefly explain how adrenaline and GPCR causes glycogenolysis

Answer 29

adrenaline activates GPCR and G protein cAMP pathway activates glycogen phosphorylase

Question 30

Briefly explain how adrenaline and GPCR causes increased gene transcription.

Answer 30

adrenaline activates GPCR and G protein cAMP pathway activates molecules for gene transcription to move into the nucleus

Question 31

Outline the stimulation pathway for cortisol production

Answer 31

ACTH release from anterior pituitary in response to CRH from hypothalamus. Stimulates cortisol production pathway in adrenal cortex

Question 32

Describe cushins syndrome

Answer 32

chronic exposure to cortisol causes decreased growth in children, weight gain, hypertension, diabetes, osteoporosis. Treatment includes adrenalectomy or steroid replacement

Question 33

What are the three main types of steroid hormones and the examples of them produced in the cholesterol pathway

Answer 33

Mineralocorticoids Glucocorticoids Androgens

Question 34

What are the three main types of steroid hormones and the examples of them produced in the cholesterol pathway

Answer 34

Mineralocorticoids: Aldosterone Glucocorticoids: Cortisol Androgens: Testosterone

Question 35

What is a nuclear receptor

Answer 35

An intracellular receptor activated by lipophilic ligands as they can diffuse across cell membrane.

Question 36

Describe the mechanism of nuclear receptor action

Answer 36

Ligand activates nuclear receptor induces homo or hetero dimerisation as well as binding of dimer to DNA Coactivator recruitment increases target gene transcription by binding to nuclear receptor Altered levels of the hormone regulated gene product produce cellular response

Question 37

What are the 2 types of estrogen receptors

Answer 37

alpha and beta

Question 38

What is ERalpha important for

Answer 38

Female reproduction mammary gland function bone, CVS, brain

Question 39

What is ERbeta important for

Answer 39

ovary, bone, brain, male prostate

Question 40

Outline a selective estrogen receptor moedulator (SERM)

Answer 40

Mimic estrogen receptor ligands to help treat disease ER agonist is BPA, stimulates over transcription causing birth defects ER antagonist if tamoxifen, which treats breast cancer, by binding to ER, preventing ER mediated gene transcription

Question 41

Briefly describe chronic myeloid leukaemia

Answer 41

caused by oncogenic tyrosine kinase called BCR-ABL overproduction and overflow of immature WBC and uncontrolled cell growth and proliferation Gleevec binds BCR-ABL preventing ATP from binding

Question 42

Briefly explain monoclonal antibodies

Answer 42

Can target cell surface receptors to stop disease by binding to receptor instead of ligand. Herceptin can bind to HER2 inhibiting activation of signalling pathways. Can be used to treat HER2 positive breast cancer.