Signal Transduction

Question 1

What is signal transduction?

Answer 1

Relay of molecular or physical signals from a cell’s exterior to its interior leading to a cellular response.

Question 2

Explain a Signal transduction..

Answer 2

1. Stimulus releases a chemical messenger in response 2. Stimulated cell diffuses chemical messenger via transport protein to it’s target cells 3. Chemical messenger binds to a receptor protein. Intracellularly if lipophillic. 4. Binding of messenger induces conformational change that elicits a response. 5. Signal is terminated

Question 3

Where do lipophilic/hydrophobic hormones bind?

Answer 3

Intracellular receptors.

Question 4

Where do hydrophilic/lipophobic hormones bind?

Answer 4

Plasma membrane receptors.

Question 5

Does a signal get stronger or weaker as it moves downstream?

Answer 5

Stronger/Amplified

Question 6

What is micro-heterogeneity?

Answer 6

Means that a single ligand can elicit multiple, but coordinated, responses within a single cell.

Question 7

How are signal transductions categorized?

Answer 7

By proximity to the target cell.

Question 8

Explain endocrine signaling and list some examples.

Answer 8

Transport of molecules (hormones) through the bloodstream. –> travel long distances. Insulin, epinephrine, thyroxine, testosterone.

Question 9

What are cytokines? Are they hormones?

Answer 9

Small signaling proteins secreted form non-glandular tissues and travel long distances. Not hormones but they travel the same way.

Question 10

What is paracrine signaling?

Answer 10

Involves transport of signal molecules from secretory cells to its neighboring cells.

Question 11

What is autocrine signaling?

Answer 11

The release of the signal from the send which contains its own target receptor.

Question 12

Explain the release and binding of Acetylcholine.

Answer 12

1. Action potential propagates through presynaptic neuron. 2. Ca++ influx into presynapse 3. ACh vesicles fuse with presynaptic membrane and release ACh into synaptic cleft. 4. ACh binds to nicotinic receptors 5. Na+ influx/ K+ outflux 6. Postsynaptic action potential 7. Nerve impulse/Muscle contraction

Question 13

What kind of channel are nicotinic receptors on?

Answer 13

Ligand-gated

Question 14

What does acetylcholinesterase do? What happens after this?

Answer 14

Breaks down ACh into choline and acetate. Choline is taken back into the presynaptic neuron to make more ACh.

Question 15

What makes up ACh?

Answer 15

Choline and Acetyl CoA/Acetate.

Question 16

What do acetylcholinesterase inhibitors do? What is an example?

Answer 16

Cause sustained skeletal muscle contraction. Neostigmine/organophosphorous

Question 17

Myasthenia gravis is an autoimmune disease, usually caused by the production of antibodies to ACh receptors, resulting in inactivation of the receptors. A drug that may help to stabilize this condition would do which one of the following? A. Stimulate the production of immune cells B. Stimulate the production of epinephrine C. Inhibit the production of acetylcholine E. Inhibit monoamine oxidase

Answer 17

D. Inhibit acetylcholinesterase

Question 18

What does an agonist do?

Answer 18

Binds to its receptor and elicits a specific response.

Question 19

What does an antagonist do?

Answer 19

Binds to a receptor and prevents binding of agonists.

Question 20

These channels often bind to neurotransmitters; the cellular response is to allow movement of ions across the cell membrane.

Answer 20

Ligand-gated Ion channels

Question 21

When ligands bind, these receptors form dimers.

Answer 21

Enzyme-linked and Cytokine receptors

Question 22

When ligand binds, these receptors activate and effector enzyme that cascades within the cell.

Answer 22

G-protein coupled receptors.

Question 23

Can signaling molecules have different receptors on different tissues? If so, what’s an example?

Answer 23

Yes, ACh on nicotinic (skeletal muscle/ligand gated ion channel) and cardiac (muscarinic/GPCR).

Question 24

Explain signal termination.

Answer 24

1. inactivation of ligand-receptor complex 2. loss of intermediates in the signaling pathway 3. return of target proteins to their original state

Question 25

What is the clinical relevance of GPCR systems?

Answer 25

Close to half of all therapeutic drugs target one GPCR system (over 1000)

Question 26

Explain the GPCR system..

Answer 26

1. Receptor binds hormone 2. G protein exchanges GTP for GDP and dissociates alpha/GTP subunit 3. Target/Effector Protein binds GTP-Gas 4. GTP hydrolyzes and Gas (alpha subunit dissociates effector protein) 5. Gas (alpha subunit) re-associates with B-y-subunit and receptor

Question 27

How is cAMP inactivated?

Answer 27

by hydrolysis via cAMP phosphodiesterase.

Question 28

What is cAMP and what does it do?

Answer 28

It is a second messenger. It activates protein kinase A (PKA) by phosphorylation.

Question 29

Colon cancer cells often contain mutations in a gene encoding a protein involved in the signaling pathway for which prostaglandin E2, a growth factor, is the agonist. Given that the prostaglandin E2 receptor activates a Gas subunit, which of the following mutations could NOT result in increased cell proliferation? A. a mutation of Gas so that its GTPase activity is lost (stimulate pathway) B. a mutation in the receptor that greatly increases its affinity for prostaglandin E2 (stimulate pathway) C. a mutation in adenylyl cylase that greatly decreases its affinity for Gas D. a mutation causing decreased activity of cyclic nucleotide phosphodiesterase (stimulate pathway, have more cAMP)

Answer 29

C. a mutation in adenylyl cylase that greatly decreases its affinity for Gas - if this happens, Gas will not bind to Adenylyl cyclase and AC cannot catalyze ATP to cAMP. This stops the amplification of the response and, in this case, seizes cell proliferation.

Question 30

What is adenylyl cyclase and why is it important?

Answer 30

AC is a transmembrane protein that catalyzes ATP to cAMP (vital secondary messenger).

Question 31

Steps of the receptor tyrosine kinase pathway?

Answer 31

1. Growth factor (ligand) binding and dimerization (exception is insulin and insulin growth factor receptors) 2. Autophosphorylation 3. Binding of adaptor proteins such as Grb2 4. Complex assembly 5. Guanine nucleotide exchange and activation of Ras 6. Ras binds to Raf and initiates the MAP kinase pathway

Question 32

Once Ras is activated, what happens?

Answer 32

1. ras-GTP activates the MAP kinase pathway 2. Further signal transduction and phosphorylation leads to a rapid activation of cytosolic proteins and also changes in gene expression.