Receptors and Cell Signaling

Question 1

Endocrine signaling

Answer 1

Hormone is transported via blood (ex: epinephrine). Used for long distance signaling. Long lasting half-life on minute scale.

Question 2

Paracrine signaling

Answer 2

Signal (paracrine factor) diffuses to neighboring target cell of a different cell type (ex: testosterone). Used for local signaling. Short-lived signals.

Question 3

Autocrine signaling

Answer 3

Secreting cells express surface receptors for its signal ex: interleukin-1). Can be growth factors in cancer cells.

Question 4

Juxtacrine/Direct signaling

Answer 4

Signal binds directly to receptor on the target cell (ex: heparin-binding epidermal GF). Common in immune cells.

Question 5

Hydrophilic signaling

Answer 5

Cannot penetrate the PM, therefore interact with receptors on cell’s surface. They employ a second messenger system.

Question 6

Lipophilic signaling

Answer 6

Can penetrate the PM and binds to a receptor inside the cell. The molecule-receptor complex acts as a transcription factor.

Question 7

Cytoplasmic receptors

Answer 7

Receptors in lipophilic signaling. Creates a hormone-receptor complex that translocates to the nucleus where it binds to a specific DNA sequence called the hormone response element (HRE) in the promoter region.

Question 8

Nuclear receptors

Answer 8

Receptors in cytoplasmic signaling. They are already present in the nucleus bound to the DNA. The hormone allows for interactions with additional proteins and actviate the complex.

Question 9

Types of receptors (3)

Answer 9

1. enzyme-coupled receptor
2. G protein-coupled receptor (GPCR)
3. ligand-gated ion channel

Question 10

Hydrophilic meds

Answer 10

Short half life and given at time of need (ex: epi).

Question 11

Hydrophobic meds

Answer 11

Long half lives and need to be taken daily (ex: oral contraceptives).

Question 12

Structural motif of GPCRs (ECD, TM, ICD)

Answer 12

1. extra cellular domain (ECD) - binds to signal
2. trans membrane domain (TM) - composed of 7 a-helices
3. intracelular domain (ICD) - interacts with G protein

Question 13

GPCR signaling overview (4)

Answer 13

1. Ligand bonds to ECD and causes a conformational change in the GCPR.
2. ICD activates its G protein by exchanging GDP for GTP.
3. Activated G protein interacts w/ membrane-bound effector (usually an enzyme that produces a second messenger) and produces a response.
4. Signal terminated.

Question 14

Guanine nucleotide exchange factor (GEF)

Answer 14

Assists in exchange of GDP for GTP.

Question 15

GTPase

Answer 15

Hydrolyzes GTP back into GDP, inactivating it.

Question 16

GTPase-activating protein (GAP)

Answer 16

Accelerates intrinsic GTPase actvity.

Question 17

Steps of G protein signal relay

Answer 17

Draw.

Question 18

Inhibitors of cGMP and cAMP PDE

Answer 18

Increased conc. of cellular cGMP, causing smooth muscle contraction and vasodilation.
Caffeine inhibits cAMP PDE, causing increased HR.

Question 19

NO and smooth muscle relaxation

Answer 19

NO produced in epithelium and is responsible to relax muscles via activation of guanylate cyclase, leading to the production of cGMP.

Question 20

Cholera toxin

Answer 20

Toxin decreased GTPase activity, causing an overproduction of cAMP. Increased cAMP in intestinal cells open Cl- channels, causing dehydration.

Question 21

Mechanism of water secretion (4)

Answer 21

1. Toxin activates AC to produce cAMP.
2. cAMP activates the CFTR.
3. Cl- secreted as a result, Na+ follows.
4. NaCl builds up and creates osmotic gradient which water follows.

Question 22

RTKs structure (3)

Answer 22

1. ECD - contains molecule binding site.
2. Single helix - spans the membrane.
3. ICD - possesses the tyrosine kinase activity.

Question 23

Gs

Answer 23

Stimulates AC.

Question 24

Gi

Answer 24

Inhibits AC.

Question 25

Gt

Answer 25

Stimulates cAMP PDE.

Question 26

Gq

Answer 26

Activates PLC.

Question 27

Gq mechanism (post GTP phosphorylation)

Answer 27

GTP activates PLC, which cleaves PIP2 into IP3. IP3 causes release of Ca2+, which causes PKC to go to membrane and is activated by DAG.

Question 28

Proteins/signal molecules involved in Gs pathway

Answer 28

AC, cAMP, PDE, PKA.

Question 29

Proteins/signal molecules involved in Gt pathway

Answer 29

cGMP, 5’-GMP, cGMP PDE.

Question 30

Proteins/signal molecules involved in Gq pathway

Answer 30

PLC, PIP2, IP3, Ca2+, DAG, PKC.