Lecture 13: Signal Transduction IV

Question 1

Beta-blockers

Answer 1

-effect Gs pathway
-norepinephrine cannot bind
= no response (pain, figh/flight)

Question 2

cAMP mediated signaling RECAP

Answer 2

1. Adenylate cyclase makes ATP to cAMP
2. cAMP subunits split into 2R+4cAMP and 2C
3. 2C (PKA) makes ATP to ADP (phosphorylyzes)
   = response

Question 3

Gaq signaling

Answer 3

1. phospholipase C-B
2. Diacylglycerol or IP3
3. PKC or IP3 receptor
4. Ca+2

Question 4

Gq

Answer 4

-muscarinic
-neurotransmitters
-acetylcholine, ANg II receptors

Question 5

Gq signaling

Answer 5

1. Ga stimulates phospholipase C-B to hydrolyze PIP2 = IP3 and DAG

Question 6

Gq signaling from IP3

Answer 6

1. IP3 gates ca2+ release from ER ion channel
2. Ca2+ binds PKC
3. PKC travels to membrane
4. PKC binds DAG and is activated

Question 7

Gq signaling from DAG

Answer 7

1. binds to PKC
2. Phosphorylate protein (add P)
3. response

Question 8

Maintaining low cytoplasmic Calcium

Answer 8

-there is more calcium outside cell (10^4 difference)
-active transport:
1. NCX:sodium-calcium exchanger (antiport)
2. Ca2+ ATPase
3. SERCA: sarco/endoplasmic reticulum Ca2+ ATPase (calcium into ER)

Question 9

Calmodulin (CaM)

Answer 9

-binds Ca2+ at 2 terminal EF hand domains (4 calcium binded 2 at each domain)
-conformational change exposes hydrophobic surfaces

Question 10

calmodulin-dependent kinase

Answer 10

-binds to alternate CaM conformation

Question 11

CaM alternate conformation (after change)

Answer 11

-binds many signaling protiens
-alters CaM kinase activity including autophosphorylation activity

Question 12

CaM + Ca2+

Answer 12

1. conformational change
2. binds protein to activate
3. autophosphorylation to fully active protein
4. lose calcium = CaM kinase
5. inactivated by protein phosphatase

Question 13

What is likely affinity of Ca2+

Answer 13

10^-6
-close to concentration

Question 14

KD of calmodulin for Ca higher than concentration of Ca

Answer 14

not binding Ca2+

Question 15

calcium increase

Answer 15

activates Gaq

Question 16

phospholipid-derived signaling

Answer 16

-phospholipase activation by GPCRs and RTKs
-hydrolyze or phosphorylate
-phospholipase C

Question 17

phospholipid receptor tyr kinases (RTK)

Answer 17

-phosphatidylinositol 3 kinase (PI3K)

Question 18

Phospholipase C hydrolysis

Answer 18

-breaks bond between glycerol and inositol of PIP2

Question 19

PIP2

Answer 19

phosphatidylinositol 4,5-bisphosphate

Question 20

DAG

Answer 20

diacylglycerol

Question 21

IP3

Answer 21

inositol 1,4,5-trisphosphate

Question 22

PLCB

Answer 22

-activated by interaction with trimeric g proteins
-GPCR

Question 23

PLCy

Answer 23

-activated by tyrosine phosphorylation
-RTK

Question 24

Phosphatidylcholine (PC) hydrolysis

Answer 24

-phospholipase D
= phosphatidic acid (PA) and choline
-PA converted to DAG

Question 25

PI3 kinase

Answer 25

-phosphorylation of 3'OH PIP2 to PIP3

Question 26

PIP3

Answer 26

-2nd messenger -recognized by pleckstrin homology domain (PH domains)

Question 27

PIP3 signaling

Answer 27

1. activated RTK + P2 + activated PI3 kinase 2. = PIP3 3. PIP3 recognized by PH domain of protein 4. =phosphorylation and activation of protein 5. dissociation

Question 28

PI3K/AKT pathway (protein Kinase B (PKB signaling))

Answer 28

-PIP3 second messenger -promotes cell survival -repress cell-death pathways -regulate glucose transport and glycogen metabolism -often altered in cancer