lectures 10-12

Question 1

hydrophilic hormone steps

Answer 1

1. bind PM receptors
2. signal transduction pathways activated
3. activate g-switch proteins/second messengers or tyrosine kinases

Question 2

hydrophobic hormone steps

Answer 2

1. diffuse through cell membrane
2. activate cytosolic receptors, move to nucleus

Question 2

effector protein

Answer 2

-usually last in signal pathway
-shuts off pathway

Question 2

endocrine signalling

Answer 2

-epinephrine, insulin
-signal carried through blood vessels to target cell

Question 2

paracrine signalling

Answer 2

-neurotransmitters, growth factors
-signal released to neighboring cells only

Question 3

autocrine signalling

Answer 3

-growth factors
-cells respond to signals they produce

Question 4

membrane protein signals

Answer 4

-direct cell to cell contact signalling

Question 5

cAMP function

Answer 5

-secondary messenger from adenylyl cyclase by phosphodiesterase
-activates PKA

Question 6

cGMP function

Answer 6

-secondary messenger from GTP by guanylyl cyclase
-activates PKG and cation channels

Question 7

IP3/DAG function

Answer 7

-secondary messenger from PIP2 by phospholipase C
-open Ca2+ channels and activate PKC

Question 8

water soluble secondary messengers

Answer 8

cAMP, cGMP

Question 9

lipid soluble secondary messengers

Answer 9

IP3, DAG

Question 10

kinase function

Answer 10

-phosphorylate proteins, activating them

Question 11

phosphorylase function

Answer 11

-dephosphorylate proteins, deactivating them

Question 12

protein kinase A activation

Answer 12

-Thr197 phosphorylated in activation loop
-promotes ATP and substrate binding

Question 13

g-protein coupled receptors function

Answer 13

-activate g proteins
-GDP -> GTP

Question 14

g-protein activity

Answer 14

-GTPase activity, hydrolyze GTP->GDP

Question 15

liver/skeletal epinephrine function

Answer 15

increase glucose concentration for energy production

Question 16

adipose tissue epinephrine function

Answer 16

breakdown triglycerides for energy production

Question 17

cardiac muscle epinephrine function

Answer 17

increase heart rate, o2 and glucose to peripheral tissues

Question 18

smooth muscle cell relaxation epinephrine function

Answer 18

increase blood flow and o2 intake

Question 19

intestine epinephrine function

Answer 19

fluid secretion

Question 20

GPCR signal transduction pathways (4):

Answer 20

1. membrane spanning helices
2. heterotrimeric g protein cycling GTP->GDP
3. effector protein
4. protein desensitizing signal pathway

Question 21

structure of GPCR’s

Answer 21

-7 transmembrane alpha helices (H1-H7)
-n-term. outside, c-term. inside
-4 extracellular segments (E1-E4)
-4 cytosolic segments (C1-C4)

Question 22

activation of effector from GPCR steps

Answer 22

1. ligand bind -> receptor conformational change 2. activated receptor binds trimeric g protein 3. GEF activity allows release of GDP from a unit 4. GTP binds -> dissociation of units b/y 5. GTP/Ga activates effector 6. GTPase hydrolyzes GTP->GDP and effector turns off

Question 23

guanine exchange factor function

Answer 23

activated receptor dissociating GDP

Question 24

GTPase-accelerating protein

Answer 24

activated effector leading to hydrolysis of GTP->GDP

Question 25

CREB activation steps:

Answer 25

1. receptor stimulation -> rise in cAMP 2. cAMP activates PKA, translocates to nucleus 3. PKA phosphorylates and activates CREB 4. activated CREB joins CBP, binds CRE on promoter 5. CREB binding allows gene transcription

Question 26

receptor tyrosine kinase ligand

Answer 26

-hydrophilic signalling molecules -cause receptor dimerization

Question 27

RAS/MAP kinase pathway overview / main proteins

Answer 27

-receptors activtate GTPase switch protein (Ras) -Grb2 and SOS recruited through SH3/SH2 domains

Question 28

guanine nucleotide exchange factors use and example

Answer 28

-SOS -release GDP

Question 29

GTPase accelerating proteins use

Answer 29

-hydrolyze GTP->GDP

Question 30

RAS kinase pathway steps (4)

Answer 30

1. SOS -> Ras 2. Ras -> Raf 3. Raf -> MEK 4. MEK -> ERC

Question 31

Ras activation steps (4)

Answer 31

1. ligand bind to RTK 2. phosphotyrosine on RTK allows Grb2 SH2 to bind 3. SH2 on Grb2 binds Pro on SOS 4. SOS releases GDP, binds GTP

Question 32

SH2 domain function

Answer 32

-bind phosphorylated Tyrosine residues

Question 33

SH3 domain function

Answer 33

-bind Proline-rich domains and motifs

Question 34

14-3-3 dimer function

Answer 34

-bound to Raf phosphoserine's and stabilize Raf

Question 35

Ras/MAP kinase pathway STEPS (5)

Answer 35

1. RTK active -> Ras-GTP 2. 14-3-3 released, Raf active 3. Raf activates MEK 4. MEK activates ERK 5. ERK activates different proteins

Question 36

MAP kinase and c-fos txn steps

Answer 36

1. MAPK activates p90, translocate to nucleus 2. p90 phosphorylate SFR 3. MAPK translocate to nucleus, phosphoorylate TCF on c-fos gene 4. c-fos transcribed

Question 37

phosphoinositide signaling pathway (PI-3) steps:

Answer 37

1. RTK activate PI-3 kinase 2. PI-3-phosphates formed which bind PH domains 3. protein kinase B activated

Question 38

active protein kinase B function

Answer 38

-inactivate pro-apoptotic proteins -synthesis of pro-apoptotic proteins

Question 39

PI-3 kinase products (3)

Answer 39

1. phosphonositol 3,4-biphosphate (IP2) 2. phosphonositol 4,5-biphosphate (IP2) 3. phosphonositol 3,4,5-triphosphate (IP3)

Question 40

PH domain of PKB function

Answer 40

1. bind PI2 2. relocate PKB to plasma membrane

Question 41

PKB activation steps ():

Answer 41

1. hormone binds, activated PI-3 kinase and PI-3 phosphates formed 2. PI-3 binds PH domains of PKB and PDK2 to partially activate 3. PDK1 phosphorylates Serines in PKB, fully activated