Lecture 2

Question 1

What does transmitting messages across the cell membrane involve?

Answer 1

conformational changes

Question 2

What are second messengers

Answer 2

are chemical signals that are not embedded in the membrane and can diffuse in the cell to pass on the message

Question 3

Give three reasons why 2nd messengers are are important chemicals for signal transduction

Answer 3

• only few receptors may be activated but each receptor produces many second messengers; this amplifies the signal
• 2nd messengers can often diffuse through the cell to other parts of the cell to influence different proteins
• multiple receptors can use common 2nd messengers allowing finely tuned regulation of cellular activity

Question 4

What are the two common 2nd messengers

Answer 4

cAMP and Ca2+

Question 5

What is the first 2nd messenger discovered

Answer 5

cAMP

by Earl Sutherland

Question 6

Which enzyme makes cAMP

Answer 6

adenylate cyclase

Question 7

true or false; cAMP are key components of GPCR signal transduction mechanisms

Answer 7

true

Question 8

Describe the G protein cycle

Answer 8

1. ) a hormone will bind to the receptor; receptor is activated
2. ) the GDP of the alpha G protein will then be replaced by GTP
3. ) the alpha G protein will dissociate from the beta-gamma dimer
4. ) will attach itself to the adenylate cyclase; an effector; activating it to start producing cAMP from ATP
5. ) the GTpase activity hydrolyses the GTP back to GDP thus eventually inactivating the G protein
6. ) when the alpha G protein is inactivated, it will then reattach itself to the beta-gamma dimer once more

Question 9

which enzyme does cAMP activate and what does it do?

Answer 9

cAMP activates protein kinase A (PKA); it is capable of phosphorylating many different proteins

Question 10

What do you call a stimulatory G protein?

Answer 10

alpha GS

increases the production of cAMP

Question 11

What do yo call an inhibitory G protein

Answer 11

alpha Gi

decreases the production of cAMP

Question 12

What does PKA do?

Answer 12

cellular response

Question 13

What is a kinase

Answer 13

catalyses the transfer of a phosphate group

Question 14

true or false; phosphorylation can either inactivate or activate a protein

Answer 14

true

Question 15

how does the cholera toxin affect the G protein?

Answer 15

• it permanently activates the G protein

- leading to excessive stimulatory adenylate cyclase and chronic elevation of cAMP levels

Question 16

why does cholera cause non stop diarrhea

Answer 16

because cAMP in epithelial cells stimulate active transport of Na+
- small intestines epithelial cells and water from the mucosal surface of the epithelial cells into the lumen of the intestines

Question 17

what happens when a hormone binds to the receptor (GPCR)

Answer 17

the receptor is activated by a hormone, which causes a conformational change in the receptor. This enables an interaction between receptor and G protein to occur

Question 18

Why does GDP depart from alpha G protein when the hormone binds to the receptor

Answer 18

the conformational change resulting from the binding of the hormone from the receptor opens up the nucleotide binding site so that the GDP can depart and GTP from solution can bind in its place

• at the same time alpha subunit departs from beta-gamma dimer

Question 19

true or false; a single activated receptor can stimulate nucleotide exchange between many G proteins, resulting in amplified response

Answer 19

true

Question 20

true or false; the G protein is heterotrimeric

Answer 20

true

Question 21

what controls phosphorylation

Answer 21

dephosphorylation by phosphotases

Question 22

what enzymes catalyze phosphorylation

Answer 22

kinases

Question 23

true or false; phosphorylation by kinases is an important mechanism for passing on messages in signal transduction processes

Answer 23

true

Question 24

What does Ca2+ depend on?

Answer 24

the release of Ca2+ from the SR in the action of the Neuromuscular junction

Question 25

Describe the steps for Ca2+ release in the cytoplasm

Answer 25

1. ) hormone binds to the receptor in the cell membrane
2. ) phospholipase C is activated
3. ) PIP2 is hydrolyzed to IP3 and DAG
4. ) IP3 is the actual second messenger
5. ) IP3 diffuses in the cytosol to the ER where it stimulates the release of Ca2+
6. ) a complex is formed between calmodulin and Ca2+
7. ) the complex activates cytosolic protein kinase

Question 26

What happens when DAG encounters PKC (protein kinase C)

Answer 26

it acts as a second messenger and activates PKC (which is responsible for Ca2+ channels; regulating Ca2+ flow in and out of the cell)