EXAM 2 - Cell Signaling

Question 1

PKA

Answer 1

-Activated by cAMP
-Phosphorylates VDCCs allowing an increase in Ca2+ entry
-Phosphorylates RYRs allowing an increase in Ca2+ entry from the SR

Question 2

DNA-PK

Answer 2

-Activated by DNA damage produced by ROS
-Phosphorylates and activates P53

Question 3

GC

Answer 3

-Activated by NO binding
-turns GTP to cGMP

Question 4

Matrix Metalloproteases (MMPs)

Answer 4

-Affect cancer cell mobility, degrades the ECM
-GoF

Question 5

CAS (Caspases)

Answer 5

-mediate apoptosis
-initator caspases activate exectutioner (effector) caspases
-Executioner caspases chop up proteins

Question 6

AngII

Answer 6

-activated by renin in the kidneys
-promotes increased contraction of vasc. smooth muscle
(activates alpha-q when bound to ATII receptor. alpha q actives PLC, PLC cuts PIP2. IP3 activates IP3 gated channels, influx of Ca2+ from the SR, Ca2+ binds to PKC. PKC binds to DAG and phosporylates VDCCs, more Ca2+ promotes increased contraction = increased arteriole resistance + decreased venous compliance = increased MAP)

Question 7

MLCP

Answer 7

-phosphorylated and activated by PKG
-dephosphorylates myosin, inhibiting contraction of smooth muscle

Question 8

Oncogene

Answer 8

-GoF mutations that promote a cancerous phenotype
-Ex: growth factor receptors, Akt, Bcl-2

Question 9

PKG

Answer 9

-Activates and phosphorylates MLCP
-Activates and phosphorylates Potassium channels allowing an efflux of K+ which leads to hyperpolarization of the cell (interferes with VDCCs on smooth muscle)

Question 10

Cas-9

Answer 10

-zymogen form = pro-caspase-9
reruited by the APAF/cyt-c complex
-when bound to the complex, pro-casp-9 undergoes cross-proteolysis leading to the active caspase-9

Question 11

cGMP

Answer 11

-Activated by GC (GTP-cGMP)
-Activates PKG

Question 12

Mdm-2

Answer 12

-Part of the intrinsic apoptotic pathway
-Activated by Akt
-Targets p53 for degradation

Question 13

Bcl-2

Answer 13

Proteins that regulate pores that allow the release of cyt-c for apoptosis
3-categories:
-pro-survival
-pro-apoptosis
-BH3 (blocks pro-survival proteins)

Question 14

PI3K

Answer 14

Turns PIP2 into PIP3
-Part of the intrinsic apoptotic pathway

Question 15

MKP

Answer 15

-Inhibits JNK (in the signaling pathway of apoptosis)
-Is activated by ROS

Question 16

AKT

Answer 16

-Activated by PIP3
-Phosphorylates and inhibits BH3
-Activates Mdm-2

Question 17

What are some Tumor Suppressor Genes?

Answer 17

P53, PTEN, BH3

Question 18

DAG

Answer 18

-Part of the cleaved PIP2
-Ca-PKC binds and activates
-This complex then activates VDCCs in smooth muscle

Question 19

Myc

Answer 19

-promotes cell proliferation (cancer!)
-activated by MAPK

Question 20

cAMP

Answer 20

-Activated by AC (ATP -> cAMP)
-Activates HCN channels
-Activates PKA

Question 21

ASK-1

Answer 21

-Activated by ROS
-Activates JNK

Question 22

RAS

Answer 22

-Activates MAPK
-monomeric G-protein

Question 23

ROS

Answer 23

-can be generated by high levels of NO
-made in the ETC
-associated with ischemia
-can cause DNA damage
-can promote apoptotic cell death

Question 24

PTEN

Answer 24

dephosphorylates PIP3 -> PIP2

Question 25

Examples of Pro-Survival/Anti-Apoptotic mutations

Answer 25

LoF of P53 GoF of Akt

Question 26

NOS

Answer 26

- Activated by Ca-CAM complex - Generates N.O.

Question 27

GRK

Answer 27

-Activated by an accumulation of beta/gamma g-protein subunits -Phosphorylates GPCRs (P leads to recruit of B-arrestin which inactivates GPCRs)

Question 28

AC

Answer 28

-Activated by Gs protein -Inhibited by Gi - When activated, generates cAMP from ATP

Question 29

2 modes of vascular control?

Answer 29

Direct = arteriole resistance Indirect = venous compliance

Question 30

PDE

Answer 30

cAMP -> AMP cGMP -> GMP

Question 31

PKC

Answer 31

-Activated when bound to Ca2+ and DAG -Phosphorylates and increases activity of VDCCs and RYRs

Question 32

P53

Answer 32

-Phosphorylated and activated by DNA-PK and JNK -Triggers cell cycle arrest when levels are low -Triggers apoptosis (via release of BH3 from nucleus) when levels are high

Question 33

PLC

Answer 33

Cleaves PIP2 to IP3 and DAG

Question 34

APAF

Answer 34

Scaffolding that binds to cyt-c and then recruits pro-caspase-9

Question 35

Rho-GTPase GoF

Answer 35

increases cancer mobility

Question 36

E-cadherin LoF

Answer 36

increases cancer cell mobility

Question 37

N.O.

Answer 37

-Produced by NOS -Can be turned into ROS in the ETC -Activates GC in smooth muscle cells

Question 38

cyt-c

Answer 38

-moves e- in the ETC -release of cyt-c from the Mt induces apoptosis

Question 39

Beta arrestin

Answer 39

-Recruited when GRK phosphorylates the GPCR -inactivates the GPCR

Question 40

Alpha-1 Adrenergic Receptor

Answer 40

-Located in smooth muscle and myocytes -NE binds to this receptor

Question 41

PIP2

Answer 41

-Cleaved by PLC into IP3 and DAG

Question 42

IP3

Answer 42

-Activated when PLC cleaves PIP2 into IP3 and DAG -Binds to IP3 gated channels on SR allowing an influx of Ca2+

Question 42

Example of a pro-proliferative mutation

Answer 42

GoF of growth factor receptors

Question 43

Ach

Answer 43

-Released from PNS -Binds to muscarinic receptors (M3)

Question 44

MLCK

Answer 44

-Activated when bound to Ca-CAM complex -Phosphorylates myosin in smooth muscle, promotes contraction

Question 44

JNK

Answer 44

-Activated/phosphorylated by ASK-1 -Activates/phosphorylates P53

Question 45

CAM

Answer 45

-Activated when bound to Ca2+ -Activates NOS to generate NO **or** -Binds to MLCK to Phosphorylate Myosin for contraction of smooth muscle

Question 45

Clathrins

Answer 45

-recuited to the GPCR/Beta-Arrestin complex -clathrin coating triggers endocytosis of GPCRs (sequestration)

Question 46

NE

Answer 46

-Released from the SNS -binds to adrenergic receptors

Question 47

VDCC

Answer 47

-depolarization allows these channels to become more active and let more Ca2+ into the cell -PKA phosphorylates VDCCs increasing activity -Ca-PKC-DAG complex phosphorylates VDCCs increasing activity

Question 48

HCN Channel

Answer 48

-allows Na+ into the cell -Activated by cAMP