Lec 3 receptors and cell signaling

Question 1

What is endocrine signaling?

Answer 1

signal is transported via blood (hormone) long distance freely diffusing signal (shorter side minutes)

Question 2

example of endocrine signaling?

Answer 2

epinephrine

Question 3

what is paracrine signaling?

Answer 3

signal diffuses to neighboring target cell of a different type Local signalling. short time

Question 4

example of paracrine signaling?

Answer 4

testosterone

Question 5

What is autocrine signaling?

Answer 5

secreting cells express surface receptors for the signal

same cell or same cell type

Question 6

example of Autocrine signaling?

Answer 6

interleukin-1

Question 7

what is direct/juxtacrine signaling?

Answer 7

signal binds to signaling cell which then binds to receptor on the target cell

Question 8

What is an example of a direct/juxtacrine signaling?

Answer 8

heparin binding epidermal growth factor

Question 9

What are the two types of signaling molecules?

Answer 9

water soluble (hydrophilic) and lipid soluble (hydrophobic)(lipophilic)

Question 10

What is the mechanism of hydrophilic signaling?

Answer 10

Cannot penetrate the membrane.

so reacts with receptors on the cell surface

This leads to production of the second messengers

Triggers a downstream response.

(shorter half life seconds to minutes)

Question 11

What receptors are involved in downstream signaling?

Answer 11

1. G-protein coupled receptors (GPCR)
2. Receptor tyrosine kinase (RTK)

Question 12

examples of hydrophilic signal molecules

Answer 12

epinephrine, insulin, glucagon

Question 13

What is the mechanism of lipophilic signaling?

Answer 13

pass through the cell membrane of target cell

ligand attaches to specific site in the cell

signaling molecule-receptor complex acts as a transcription factor (regulates transcription of specific genes)

long-acting hours to days

(steroids)

Question 14

Where are the locations of lipophilic signaling receptors?

Answer 14

Cytoplasmic receptors

nuclear receptors

Question 15

how do cytoplasmic receptors work?

Answer 15

in an inactive from of HSP 90

upon binding of ligand HSP dissociates

hormone receptor complex then goes to nucleus

binds DNA sequence hormone response element (HRE)

(promoter region of genes)

Question 16

How do nuclear receptors work?

Answer 16

already in nucleus bound to DNA

protein bind allows addition of additional proteins and activates

Question 17

Types of receptors?

Answer 17

Question 18

What is the structure of a G-coupled protein receptor? (GCPR)

Answer 18

Question 19

Steps of G protein signal relay

Answer 19

1. ligand binds to receptor
2. conformational change occurs in receptor
3. GPCR able to interact with and bind G protein
4. RECEPTOR THEN ACTS AS A GEF (GUANIDINE EXCHANGE FACTOR)
5. conformation of Galpha protein is changed such that it kics out GDP and GTP binds
6. Galpha actived and binds and activates or inhibits effector mol
7. effector mol catalyzes reactions that produce secondary molecules

Question 20

What is GAP and what does it do?

Answer 20

GTPase activating protein

accelerates the hydrolyzing of bound GTP to GDP and phosphate.

Question 21

Gs GPCR signal

Answer 21

Stimulates adenylate cyclase (makes cAMP)

cAMP activates protein kinase A

Phosphylation via PkA

Question 22

Gi GPCR signaling

Answer 22

Inhibits adenylate cyclase

no cAMP produced

so PKA not activated so no phosphorylation

Question 23

Gt GPCR signaling

Answer 23

(uses light (photons)) (T for Tan)

stimulations cGMP phosphodiesterase

breaks down cGCP to 5’-GMP

turns off something that was already on

Question 24

Gq GPCR signaling

Answer 24

activates phospholipase C

activates PIP2

makes DAG

which activates PKC

phosphorylation of target proteins

(IP3 releases Ca2+ which helps activate PKC and also

activates CA calmodulin complex)

Question 25

what binds to activate Gs protein

Answer 25

epinephrine (Beta-adrenergic receptor) and histamine

Question 26

examples of what binds to activate Gi protein

Answer 26

epinephrine/norepinephrine (alpha-adrenergic receptor) Dopamine

Question 27

examples of what binds to activate Gq protein

Answer 27

acetylcholine

Question 28

Examples of what binds to activate Gt protein?

Answer 28

Light (photons)

Question 29

Epinephrine and G proteins

Answer 29

non-selective agonist of all adrenergic receptors (alpha 1, alpha 2, beta 1, beta 2, beta 3 multiple GPCR signaling pathways

Question 30

Can G protein-coupled receptors have multiple responses?

Answer 30

Question 31

what hydrolyzes cAMP and cGMP

Answer 31

cAMP/ cGMP phosphodiesterase

Question 32

what can inhibition of cGMP phosphodiesterase cause?

Answer 32

can cause increase in cGMP due to no hydrolyze leads to smooth muscle relaxation and vasodilation (Viagra, levitra, cialas)

Question 33

NO causes what?

Answer 33

diffuses in muscle and activated guanylate cyclase smooth muscle relaxation and vasodilation nitrates lower blood pressure Dont take with cGMP PDE inhibitor or too low BP

Question 34

Mechanism of Cholera

Answer 34

Gs contaminated water covalent modification of alpha subunits ADP ribosylation of Arg decreases GTPase activity Gs(alpha) remains active stims adenylate cyclase too much cAMP cells open Cl- channels Na+ soon follows loss of water/electrolytes

Question 35

Mechanism of Pertussis

Answer 35

Gi ADP ribosylation of Cys on Gi(alpha) prevents alpha unit dissociation in G protein complex less inhibition of AC and overproduct cAMP loss of fluids and excessive mucous in airway epithelial cells (Cl- ion out Na+ follows then water)

Question 36

Signal desensitization

Answer 36

Question 37

What does a G protein receptor kinase do?

Answer 37

(GRKs) phosphorylate GPCRs (ATP used) arrestin binds 3rd intracellular loop prevents Galpha interact with loop Galpha-GDP does not get converted to Galpha-GTP inactive G protein complex