Cell Signaling

Question 1

What are ACE-inhibitors? How do they work?

Answer 1

1) drug that controls blood pressure
2) blocks angiotensin converting enzyme (ACE) from converting angiotensin I into angiotensin II

Question 2

What are the 3 modes of actions for chemical messengers?

Answer 2

1) endocrine (thru blood)
2) paracrine (adjacent cell)
3) autocrine (same cell)

Question 3

What are the 3 types of plasma membrane receptors?

Answer 3

1. ion channel receptor
2. receptor kinases
3. heptahelical receptors

Question 4

What are the 5 classes of chemical messengers, and what are their functions?

Answer 4

1. neuropeptides: nervous sys
2. hormones: endocrine sys
3. cytokines: immune sys
4. eicosanoids: injury
5. growth factors: cell proliferation

Question 5

Define second messengers.

Answer 5

non-protein molecules that amplify cell signal, have ability to diffuse, and have a fast response relative to proteins that turn genes on

Question 6

What is the sequence of cell signaling steps?

Answer 6

chemical messenger –> cell receptor –> signal transducer proteins –> second messengers –> effector activation –> termination of signal

Question 7

Describe the intracellular signaling pathway. Example?

Answer 7

lipophilic chemical messenger –> diffuses across PM –> binds to receptor in cell –> increased gene transcription; ex. cortisol

Question 8

What are the 3 types of second messengers?

Answer 8

1) phosphatidylinositol (PIP) signaling 2) cAMP 3) Ca2+

Question 9

What do kinases & phosphatases do?

Answer 9

1) kinase: phosphorylate 2) phosphatase: remove phosphate

Question 10

Describe the ion channel receptor pathway. Example?

Answer 10

1) chemical messenger binds to PM receptor –> channel opens, allowing Na+ ions to flow into cell 2) nicotinic acetylcholine receptor

Question 11

Describe the INF or IL/JAK/STAT kinase signaling pathway.

Answer 11

cytokine binds receptor –> JAKs dimerize & cross-phorylate & phosphorylate tyrosine on receptor –> SH2 chemical messenger (STAT) binds to tyrosine –> JAKs phosphorylate STATs as well –> STATs dissociate, dimerize –> bind DNA, turn genes on

Question 12

Describe the TGF-beta receptor kinase signaling pathway.

Answer 12

1) heterodimer receptor (I & II) –> TGF-bta binds to II, serine on type I kinase is phosphorylated –> R-Smad phosphorylated –> Smad activates Co-Smad –> bind DNA, turn on genes

Question 13

What can mutations in RAS cause?

Answer 13

Cancer

Question 14

Describe the tyrosine kinase (EGF) signaling pathway.

Answer 14

GF binds to homodimers, tyrosine kinases dimers autophosphorylate

–> SH2 chemical messenger protein (Grb2) binds

–> SOS protein binds

–> Ras small G-protein binds –> exchanges GDP for GTP to activate its kinase domain

–> binds Raf (MAPKKK) –> MAPKK –> MAPK –> transcription factor

Question 15

Explain the steps for PI3 pathway in insulin receptors.

Answer 15

Phosphatidylinositol phosphorylated to make PIP2

–> phosphoyrlated by PI3 –> PIP3

–> joins w/ PDK1 –> Akt / activates PKB

Question 16

Describe the tyrosine kinase (insulin receptor) signaling pathway.

Answer 16

alpha and beta subunits on receptor –> insulin binds

–> kinase domain is autophosphorylated

–> IRSs are phosphorylated

–> SH2-containing proteins can bind to IRS (Grb2 / PLC-gamma/ PI3 kinase)

Question 17

Describe the kinase receptors signaling pathway. What are the 4 examples?

Answer 17

1) receptor activated –> associated kinase phosphorylates –> signal transducer protein binds to kinase
2) Serine/threonine receptors (TGF-beta); INF or IL/JAK/STAT; Tyrosine receptors (EGF & Insulin)

Question 18

What’s one result of insulin receptor signaling?

Answer 18

increases number of glucose transporters at the plasma membrane

Question 19

How does the cAMP second messenger pathway work downstream of beta-adrenergic receptor?

Answer 19

norepinephrine binds to receptor

–> –> activated G protein helps adenylyl cyclase catalyzes the conversion of ATP to cAMP

–> binds to regulatory subunit of PKA to activate it

–> glucose production in muscle & liver

Question 20

Describe the heptahelical (G-protein Coupled) receptor pathway. Examples?

Answer 20

1) 7 alpha helices form barrel in membrane w/ hetero-trimeric G-proteins as associated signal transducers –> GDP exchanged for GTP & activates G-proteins –> cAMP or DAG/IP3 second messenger pathways
2) beta-adrenergic receptors, angiotensin receptors

Question 21

What are beta-blockers? How do they work?

Answer 21

1) drugs used to treat cardiac arrhythmia
2) bind to beta-androgen receptor (compete against norepinephrine)

Question 22

How does the cAMP signal get terminated?

Answer 22

cAMP phosphodiesterase reduces cAMP levels by hydrolyzing cAMP to AMP

Question 23

How does cholera toxin affect the G-protein signaling pathway?

Answer 23

G-alpha-s subunit is covalently modified so that it can’t hydrolyze GTP-GDP

• -> Adenylyl Cyclase cannot be turned off
• -> cAMP is constantly being made

Question 24

What are the subunit types of G-alpha proteins & what do they do in downstream pathway?

Answer 24

1) s –> stimulates adenylyl cyclase (cAMP)
2) i/o –> inhibits adenylyl cyclase
3) t –> stimulates cGMP phosphodiesterase
4) q/11 –> activates phospholipase C-beta (IP3, DAG)
5) 12/13 –> alters cytoskeletal elements

Question 25

How does the IP3 / DAG second messenger pathway work downstream of angiotensin receptor?

Answer 25

angiotensin II binds to receptor –> –> activated G protein helps phospholipase C cleave PIP2 into DAG and IP3 –> IP3 opens Ca2+ channel in ER to increase Ca2+–> DAG & Ca2+ activate protein kinase –> other proteins phosphorylated

Question 26

How does pertussis toxin affect the G-protein signaling pathway?

Answer 26

1) causes G-alpha-i to remain off indefinitely 2) causes covalent modification of G-alpha-i so that it can’t bind to GTP –> causes increase in cAMP

Question 27

How can cell signals be terminated?

Answer 27

1) messengers no longer secreted or degraded 2) receptor desensitized 3) phosphatases 4) GTPases 5) phosphodiesterases