5: Cell Signaling

Question 1

hydrophilic vs lipohphilic signaling

Answer 1

Hydrophilic: cannot pepetrate cell membrane; receptors are on cell surface
Lipophilic signaling: can cross through cell membrane and bind receptor inside cell

Question 2

Three things that use hydrophilic signaling

Answer 2

Insulin, glucagon, epi

Question 3

Purpose of Lipophilic signaling

Answer 3

Regulate transcription of specific genes

Question 4

Cytoplasmic lipophilic receptor signaling: three steps

Answer 4

1. Are inactive/complexed with HSP90
2. Ligand binds-> HSP dissociates
3. Hormone-receptor complex goes to nucleus -> binds HRE (hormone response elements)

Question 5

Nuclear lipophilic receptor signaling: basic flow

Answer 5

Hormone binds receptor -> allows for interactions with additional proteins -> activates complex

Question 6

Three examples of lipophilic signals

Answer 6

Steroid hormones, thyroxine, retinoids

Question 7

Which ligands have longer half lives - hydrophilic or lipophilic?

Answer 7

Lipophilic

Question 8

Three domains of a GPCR and RTK

Answer 8

1. Extracellular domain
2. Transmembrane domain
3. Intracellular domain

Question 9

Structure differences between GPCR and RTK

Answer 9

GPCR: 7 alpha helices spanning membrane
RTK: single helix spanning membrane

Question 10

How GPCR signaling is terminated by a drop in [H]

Answer 10

Decreased adenylyl cyclase -> decrease cAMP -> decreased PKA

Question 11

How does heterotrimeric G protein become active?

Answer 11

Must exchange GDP for GTP

Question 12

GAP

Answer 12

GTP-ase activating protein; accelerates GTPase activity

Question 13

What part of GPCR acts as a GTPase?

Answer 13

G protein

Question 14

Two examples of Gs GPCR signaling

Answer 14

Epinephrine, histamine

Question 15

Two examples of Gi GPCR signaling

Answer 15

Epi, dopamine

Question 16

Example of Gq GPCR signaling

Answer 16

Acetylcholine

Question 17

Two types of downstream activities of RTK signaling

Answer 17

1. RAS dependent

2. RAS independent

Question 18

What family of protein kinases facilitates RAS-dependent signaling?

Answer 18

Mitogen-activated protein kinase (MAPK)

Question 19

What is neurofibromatosis associated with

Answer 19

Defects in RAS dependent RTK signaling

Question 20

Drug example that involves RTKs

Answer 20

Breast cancer drug Herceptin -> targets HER2 (an RTK)

Question 21

Other name for monomeric G proteins

Answer 21

Small G proteins

Question 22

Important role of monomeric G proteins

Answer 22

Transduction of signals from membrane receptor to effector

Question 23

Structure of monomeric G proteins

Answer 23

Single polypeptide chain

Question 24

Intrinsic property of monomeric G proteins

Answer 24

Intrinsic GTPase activity

Question 25

Four subfamilies of monomeric G proteins

Answer 25

RAS, RAB, RHO, RAN

Question 26

What do cAMP and cGMP phosphodiesterases do?

Answer 26

Break cAMP and cGMP into AMP and GMP

Question 27

Effect of cGMP PDE inhibitors

Answer 27

Increases cGMP concentration -> smooth muscle relaxation and vasodilation -> erection

Question 28

Example of cAMP PDE inhibitor + three cGMP inhibitors

Answer 28

CAMP PDE inhibitor: caffeine

CGMP PDE inhibitor: VIagra, Levitra, Cialis

Question 29

Cholera toxin: 3 steps in action

Answer 29

1. Prevents inactivation of Gs alpha subunit by decreasing intrinsic GTPase activity
2. Continuously stimulates adenylate cyclase -> overproduction of cAMP
3. Opens extra Cl channels -> loss of electrolytes and water -> diarrhea

Question 30

Cystic fibrosis mechanism

Answer 30

Toxin activates adenylate cyclase -> cAMP -> activates CFTR -> Cl secretion -> followed by Na secretion -> followed by water secretion

Question 31

Pertussis mechanism

Answer 31

Toxin prevents activation of Gi alpha -> less inhibition of adenylate cyclase -> overproduction of cAMP in airway epithelia -> loss of fluids and mucous secretion -> Whooping Cough

Question 32

What does Nitric Oxide do in muscles

Answer 32

Activates guanylate cyclase -> production of cGMP -> smooth muscle relaxation and vasodilation

Question 33

Why should you not take viagra and nitroglycerin simultaneously?

Answer 33

They both lead to vasodilation

Question 34

Antihistamines

Answer 34

Block GPCR that binds histamine