#3

Question 1

What are the 4 types of signaling receptors?

Answer 1

1. Ligand activated ion channels
2. G protein coupled receptors
3. Tyrosine kinase receptors
4. Ligand activated transcription factors

Question 2

About 40% of all drugs are directed agonists or antagonists of one which type of receptor?

Answer 2

G protein coupled receptor

Question 3

_______ produce graded potential (local effects).

Answer 3

Ligand activated ion channels in the plasma membrane.

Question 4

How does depolarization occur?

Answer 4

Ligand activated ion channels let sodium in to cell.

Question 5

How does Hyperpolarization occur?

Answer 5

Ligand activated ion channels let Cl- in to cell.

Question 6

What is considered the basis of synaptic transmission of nerve impulses?

Answer 6

The activating and inhibiting ligand activated plasma membrane ion channels. (Hence many drugs target here)

Question 7

How do drugs act on synaptic transmission? (4 main ways)

Answer 7

1. Mimic or block the actions of NT’s to affect synaptic transmission.
2. Some drugs might block the channel to affect synaptic transmission.
3. Some drugs might affect transmitter reuptake. (Block it so effect of NT is prolonged)
4. Some drugs might affect transmitter metabolism.

Question 8

What are Ligand activated channels in the Organelles?

Answer 8

IP3-mediated Ca+ release from the ER.

*This receptor mediates Ca++ release from the ER internal store.

Question 9

What is MOST signaling by Ca++ mediated by?

Answer 9

Ca++/Calmodulin complex

Question 10

What occurs during an increase in Ca++?

Answer 10

Increases binding of Ca++ to Calmodulin, altering the structure of the Ca ++/calmodulin complex

Question 11

What does the Ca++/Calmodulin complex do?

Answer 11

Activates numerous effector proteins such as:

• Calcium/calmodulin dependent protein kinase
• Nitric oxide synthase

Question 12

How do Agonists activate G-protein coupled receptors?

Answer 12

Agonists bind to the GPCR’s, alter the proteins conformation, leading to the activation of a trimeric G protein.

Question 13

What are the 4 steps of the G- Protein Cycle?

Answer 13

1. Ligand bound GCPR stimulates GDP-GTP exchange.
2. This causes the complex to fall apart into two pieces; G-alpha and G-betaG-Gamma.
3. The G-alpha has an intrinsic GTPase activity Eventually the GTP is hydrolyzed to GDP and Pi. RGS proteins accelerate this process.
4. After GTP hydrolysis the complex reassembles.

Question 14

Does G-alpha or G-BetaG-Gamma participate in signaling events?

Answer 14

Both!

Question 15

What is the major signaler in cells?

Answer 15

The liberated G-alpha protein.

Question 16

What is the Minor signaler in cells?

Answer 16

The liberated G-betaG-gamma protein

Question 17

There are ____ different classes of G-alpha proteins based on _____.

Answer 17

5 different types

Based on what they activate.

Question 18

Most important class of G alpha proteins is….

Answer 18

G-alpha S

Question 19

What is the most important function of cAMP?

Answer 19

Binds to regulatory substances releasing and activating protein kinase A (Active catalytic subunit)

Question 20

What occurs when PKA (or other protein kinases) phosphorylate transcription factors?

Answer 20

Changes in gene expression

Question 21

What are the Major effectors of G-alpha’s?

Answer 21

Signaling molecules embedded within phospholipids in the membrane. G protein coupled receptors liberate them by activating phospholipases.

• Phospholipase C beta

Question 22

_______ is the source of eicosinoid signaling molecules.

Answer 22

Arachidonic acid

Question 23

What are the products of Phospholipase C-beta mediated hydrolysis? What is the importance of them?

Answer 23

• Diacyl glycerol (DAG)
• Inositol (3,4,5)-Triphosphate (IP3)

*Both are important signaling molecules

Question 24

________ serves as the substrate for phospholipase C.

Answer 24

Phosphatidylinositol-4,5 bis phosphate (PIP2)

Question 25

Cleavage of PIP2 by phospholipase C yields ________ and _________.

Answer 25

- DAG | - IP3

Question 26

What are 2 examples of proteins activated by the Ca/calmodulin complex?

Answer 26

1. Calcium/Calmodulin dependent protein kinase | 2. Nitric oxide synthase

Question 27

__________ Activates protein kinase C.

Answer 27

DAG | *DAG allows the enzyme to bind Ca++ tighter therefore enzyme can function at lower Ca++ concentrations.

Question 28

______ plays a critical role in turning off the GPCR.

Answer 28

G-beta/G-gamma complex. | *Helps localize the trimeric G protein to the membrane

Question 29

The trimeric G protein gets turned on by _______.

Answer 29

agonist-GPCR complex. | *Trimeric G protein then turns itself off and Agonist-GCPR complex is free to activate other trimeric G-proteins.

Question 30

What does IP3 do?

Answer 30

Activates Ca++ release from ER...Which ends up activating PKC?

Question 31

What Does DAG do?

Answer 31

Activates PKC

Question 32

After trimeric G protein gets turned on by agonist-GPCR complex, does the signal stay around?

Answer 32

No! The receptor gets turned off by a process called desensitization!

Question 33

What is desensitization and how does it take place?

Answer 33

Desensitization is where GPCR's are endocytosed.

Question 34

Endocytosed receptors (during desensitization have 2 fates, what are they?

Answer 34

1. Recycled | 2. Degradation

Question 35

Why is receptor desensitization important in pharmacology?

Answer 35

B/C sometimes drugs are administered chronically and this can lead to loss of responsiveness to the drug and results that would seem paradoxical if one failed to consider desensitization.

Question 36

Describe the process of signaling by receptor tyrosine kinases....(

Answer 36

1. Receptors either contain an intrinsic tyrosine kinase enzyme or an extrinsic tyrosine kinase enzyme. 2. Binding of the ligand leads to dimerization of the receptor. 3. Some receptors form homodimers, some from heterodimers, some form both. 4. Dimerization leads to transphosphorylation of receptors. 5. Tyrosine phosphorylation of receptor leads to docking of signaling molecules. 6. the positioning of proteins near the membrane leads to different cascades of signaling. * MAP kinase cascade is an example of this signaling cascade

Question 37

What does Akt signaling do?

Answer 37

Pushes cell toward growth and expansion phase.

Question 38

Describe JAK-STAT signaling (signaling cascade) 5 steps...

Answer 38

1. Binding of ligand (cytokine) leads to phosphorylation of receptor by JAK kinase. 2. This leads to binding of STAT protein (one of six) to the phosphorylated receptor. 3. This leads to phosphorylation of STAT protein by JAK kinase. 4. This leads to dimerization of STAT protein. 5. This leads to translocation of STAT dimer to nucleus and transcriptional activation of panels of genes.

Question 39

When does a STAT become active?

Answer 39

After forming a dimer with another STAT. | *STAT's are phosphorylated at their SH2 domain.

Question 40

What does JAK-STAT signaling cause?

Answer 40

Transcriptional activation of panels of genes.

Question 41

What is the importance of JAK-STAT signaling?

Answer 41

It is the single most important pathway in which cytokines work!

Question 42

How many STAT proteins are there?

Answer 42

6

Question 43

Why are STAT proteins important? What do they do?

Answer 43

STAT proteins form different dimers which bind to different receptors which activates different panels of genes which mediate the biological responses to cytokines.

Question 44

Phosphorylation of transcription factors by PKA and other kinases can lead to ____________.

Answer 44

changes in gene expression!

Question 45

What is Cross talk?

Answer 45

The ability amongst some pathways to create complex signaling possibilities.

Question 46

What are Nuclear Hormone receptors?

Answer 46

``` Receptors for steroids such as: Glucocorticoids Mineralocorticoids Testosterone Estrogens and Progesterones and other molecules ... ```

Question 47

What is a class 1 nuclear receptor?

Answer 47

Exist as a complex with heat shock proteins in the absence of ligand.

Question 48

What do Class 1 Nuclear receptors do?

Answer 48

Ligand binding to the complex induces it to fall apart and from a homodimer and bind to specific DNA Response element. Once bound, it binds coactivators to stimulate transcription. *Ligands for receptor are glucocorticoids, progesterones estrogens and androgens.

Question 49

What is a class 2 Nuclear receptor?

Answer 49

A receptor that binds to DNA at its specific response element in the ABSENCE of a ligand.

Question 50

What do class 2 nuclear receptors do?

Answer 50

Bind corepressors in the absence of a ligand to repress transcription. *Form homo and heterodimers

Question 51

_______ acts as a switch to change from binding corepressors to coactivators and so changing from inhibiting transcription to activating it.

Answer 51

Ligand binding