Receptors And Cell Signaling

Question 1

What are the two types of signals?

Answer 1

Water soluble
-hydrophilic

Lipid soluble
-hydrophobic

Question 2

Epinephrine, insulin, and glucagon are examples of what time of signaling that initiates production of a second messenger, and has a shorter half life

Answer 2

Hydrophilic signaling

Question 3

What are two receptors involved in hydrophilic signaling

Answer 3

G-protein couple receptors and receptor tyrosine kinase

Question 4

Steroid hormones, thyroid hormones, and retinoids are examples of what type of signaling that binds to receptors proteins inside the cell and create a transcription factor from the molecule-receptor complex

Answer 4

Lipophlic signaling (hydrophobic)

Question 5

Where can lipophilic signaling receptors be located

Answer 5

Cytosol or nucleus

Question 6

_____ exist in an inactive complex with HSP90. Upon binding of signal, the HSP dissociates and the receptor complex translocates to the nucleus where it binds to a specific DNA sequence called the HORMONE RESPONSE ELEMENT in the promoter region

Answer 6

Cytoplasmic receptors
(Hydrophobic signaling)

*regulates transcription of genes

Question 7

_____ receptors are already present in the nucleus and are bound to DNA awaiting for a signal to be activated

Answer 7

Nuclear receptors
-hydrophobic signaling

-regulates transcription of genes

Question 8

Explain the structural motifs of G-Protein coupled receptors (GPCRs or 7TM receptors)

Answer 8

**heterotrimeric / hydrophilic

1. extra cellular domain-binds to signal
2. Transmembrane domain-composed of 7 alpha helixes
3. Intracellular domain-interacts with G proteins

Question 9

The intracellular domain of a GPCR activates the G protein by triggering what

Answer 9

Exchange of GDP—> GTP

Question 10

An activated GTP-bound G protein interacts with a membrane-bound _________, usually producing a second messenger

Answer 10

Effector protein/ effector enzyme

Question 11

Where is the GDP bound in inactive G proteins

Answer 11

To the alpha subunit which is attached To the beta and gamma subunits of the trimeric protein (has alpha, beta, and game subunits)

Question 12

The activation of G proteins by exchange of GDP to GTP occurs via the action of _____

Answer 12

GEF
Guanine nucleotide exchange factor

*The GTP binds to the alpha subunit that then dissoates from the beta and gamma subunit of the trimeric protein

Question 13

What is the function of intrinsic GTPase activity in G proteins? And what can accelerate its function?

Answer 13

Intrinsic GTPase activity returns the G protein to its inactive state by hydrolyzing the GTP to GDP

It can be accelerated by GTPase-activating protein (GAP)

Question 14

7 simple steps of a G protein signal relay

Answer 14

1. (Hydrophilic signal) ligand binds to GPCR
2. Conformational change to GPCR
3. GPCR able to interact and bind with the G protein inside of the cell
4. Receptor than acts as a GEF and exchanges GDP for GTP
5. Alpha subunit dissociates form other subunits
6. Activated alpha subunit binds to activate or inhibit effector protein
7. Effector molecule catalyzes reactions that produce secondary messengers, GTP hydrolyzes

Question 15

Explain GPCR signaling via Gs pathway

Answer 15

1. The activated GTP-bound alpha subunit activate adenylate cyclase (AC)
2. AC converts ATP —> cAMP
3. CAMP activates PKA
4. PKA phosphorylates Target proteins and alters activity

Question 16

Explain GPCR signaling via GI pathway

Answer 16

1. Activated GTP-bound alpha subunit inhibits adenylate cyclase (AC) activity
2. Inhibition of AC results in no cAMP production or activation of PKA

Question 17

Explain GPCR signaling via the Gt pathway

Answer 17

1. The primary signal comes from light (the g -protein is rhodopsin)
2. Activated GTP-bound alpha subunit activates cGMP phosphodiesterase
3. CGMP PDE converts cGMP—> 5’-GMP
4. Important for vision

Question 18

Explain the GPCR signaling pathway via Gq pathway

Answer 18

1. Activated GTP-bound alpha subunit activates PLC which makes PIP
2. PIP goes on to make DAG and IP3
3. IP3 activates a calcium channel that release calcium from the ER/SR
4. Release Ca2+ activates the Ca2+calmodulin-complex which then activates calmodulin dependent proteins
5. DAG activates PKC which phosphorylates target proteins and alters activity

Question 19

Epinephrine and histamine utilizes which specific GPCR pathway

Answer 19

Gs

Question 20

Epinephrine/ norepinephrine and dopamine utilize what GPCR specific pathway

Answer 20

GI

Question 21

Acetylcholine uses what GPCR specific pathway

Answer 21

Gq

Question 22

Light signals use what GPCR specific pathway

Answer 22

Gt

Question 23

What hormone can be administered to relieve bronchospasms during an asthma attack or to restore cardiac rhythms after cardiac arrest

Answer 23

Epinephrine

Which can follow a Gs or GI pathway

Question 24

What is the function of cAMP phosphodiesterase

And cGMP phosphodiesterase

Answer 24

Hydrolyze cAMP -> AMP

Or hydrolyze cGMP -> 5’-GMP

Question 25

What happens when cGMP PDE and cAMP PDE is inhibited

Answer 25

CGMP-PDE inhibition (by viagra) increases cGMP levels which causes smooth muscle relaxation and vasodilation

CAMP-PDE inhibition (by caffeine) leads to increased heart rate

Question 26

What is produced by epithelial cells to promote relaxation of smooth muscle and vasodilation by producing cGMP

Answer 26

Nitric oxide (NO)

• there some patients take nitrates to lower blood pressure
• patients should not take nitrates and cGMP PDE inhibitors at same time bc it can cause fatal drops in BP

Question 27

What does Cholera toxin do to G-protein signaling

Answer 27

-prevents inactivation of Gs
-from covalent modification of alpha subunits ADP ribosylation of Arginine which decreased GTPase activity
(Resulting in over production of cAMP which causes intestinal cells to open Cl- channels which causes loss of water and diarrhea)

*contaminated water

Question 28

What does Pertussis (whopping cough) do to g- proteins

Answer 28

-prevents Gi activation
(Resulting in overproduction of cAMP causing loss of fluid and excessive mucous in airways)

-ADP ribosylation of cystine causes dissociation of alpha subunit

Question 29

What is the function of G-Protein Receptor Kinases (GRKs)

Answer 29

GRK’s phosphorylates GPCR’s

This causes:

1. Arrestin to bind to the 3rd loop of the phosphorylated GPCR
2. Alpha subunit can not bind to 3rd loop now
3. Results in inability to convert GDP to GTP there for inactive complex

**impairs downstream reactions of GPCRS

Question 30

Describe the structural motif of Receptor Tyrosine Kinase (RTK)

Answer 30

• extracellular domain binding site (signals tend to be growth factors)
• single alpha-helical transmembrane domain monomeric)
• intracellular domain holds tyrosine kinase activity

Question 31

The binding of a Ligan to RTK extracellular domain causes what

Answer 31

Dimerization (which triggers TK activity )

-dimerized receptors phosphorylate tyrosine residues

Question 32

Phospho-tyrosines recognized by adaptor and docking proteins (SH2 domain of Grb2) activate downstream signaling pathways of _____

Answer 32

RAS-dependent (MAPK pathway)

And

RAS-independent (other kinase pathway)

*both trigger phosphorylation of specfic protein targets which affect transcription and activity of genes

Question 33

Adaptor proteins GRB-2 and IRS-1 have domains called ___ and ____ which recognize and bind to motifs receptors with phosphorlayted tyrosines

Answer 33

SH2 and PTB

Question 34

T/F

RTK’s need additional GEF’s to come in to convert GDP to GTP

Answer 34

True because it is monomeric

Question 35

RAS-dependent signaling is facilitated by what

Answer 35

Mitogen-activated protein kinase (MAPK)

Question 36

Insulin signaling via RTK

Answer 36

IRS-1 binds to GRB-2 (RAS-DEP) or P13-kinase (RAS-INDP)

RAS DEP:

• alters gene transcription
• increases glucokinase

RAS INDP:

• alters protein/enzyme
• increases GLUT4 movement