Cell Signaling I (Sept. 11 - Simmons)

Question 1

What two components are necessary to transduce a signal?

Answer 1

1. Signaling molecule

2. Corresponding receptor

Question 2

What are the types of signaling 5 general types of signaling

Answer 2

1. Autocrine
2. Paracrine
3. Contact dependent
4. Synaptic
5. Endocrine

Question 3

Describe autocine signaling

Answer 3

Cell secretes its own signaling factors that effects itself

Question 4

Describe paracrine signaling

Answer 4

Cell secretes signaling molecules that affect cells with receptors only in local area

Question 5

What is contact dependent signaling?

Answer 5

When a cell usually containing a signaling molecule in its plasma membrane docks/contacts another cell with the receptor and causes the signal to be transduced

Question 6

Describe synaptic signaling

Answer 6

Usually at the end of axons (affecting other nerves or a target cell). Signaling molecules must diffuse into space and cross a junction in order to bind the receptor. (Neurotransmitters)

Question 7

What is endocrine signaling?

Answer 7

Systemic signaling - usually occurs when hormones are secreted into bloodstream on a diffuse level. Slow to effect but prolonged. Affects target cells downstream

Question 8

How is it that cells do not universally respond to signaling molecules the same way?

Answer 8

Each cell contains or may lack specific receptor domains for each signaling molecules ensuring specific responses to different molecules

Question 9

Describe how cells can use multiple signaling molecules to decide what to do?

Answer 9

Different signaling molecules and their combinations dictates to a cell whether they should grow, divide, differentiate, or undergo apoptosis.
(additive signal transduction)

Question 10

True/False: A signaling molecule may have different effects depending on the target cell

Answer 10

True. Acetylcholine works in different ways to produce different responses in different tissues. Multiple receptors exist for each signal

Question 11

Signaling molecules which are found floating throughout the bloodstream are usually ______ and cannot _______ the cell

Answer 11

1. hydrophilic

2. enter

Question 12

Hydrophobic signaling molecules have to have this when in the blood stream…

Answer 12

What is a carrier protein

Question 13

What is the most common type of hormone that affects nuclear receptors

Answer 13

Steroid hormones

Question 14

How do steroid hormones work to elicit an effect in cells?

Answer 14

• Diffusion into cell
• Binding to steroid receptor (transcription factors)
• Activation of said transcription factor
• Induction of primary-response proteins

Question 15

What are the differences between primary-reponse and secondary-response proteins?

Answer 15

Primary response proteins may either repress primary receptors or go on to turn secondary response genes.
Secondary response proteins are created from primary response protein signals. (referred to as delayed response to hormones)

Question 16

Nuclear receptor superfamilies all have this motif in common

Answer 16

DNA binding domain

Question 17

Nuclear signaling receptors usually have a _______ protein at C-terminus and a _______ binding domain.

Answer 17

1. inhibitory

2. ligand

Question 18

Describe what happens when a ligand binds to a nuclear receptor

Answer 18

-Inhibitory protein released
-Recruitment of coactivator protein
(binds transcription activating domain and ligand)
-Binding to DNA of receptor
-expression of target genes

Question 19

What are the two classes of cell-surface receptors?

Answer 19

• Ion-coupled channels

- Enzyme-coupled receptors

Question 20

How do enzyme-coupled receptors work?

Answer 20

Signaling molecule- in form of a dimer binds to receptors
Causes association of transmembrane receptors and either
1. Activation of their catalytic domains
OR
2. Activation of associated protein

Question 21

G-protein-coupled receptors are a major part of _____ interaction. Over _____% of them bind to these receptors.

Answer 21

1. Drug/medicine

2. 50%

Question 22

Describe the critical structure of G-protein receptors

Answer 22

• 7 transmembrane passes
• Receptor N- terminal domain (usually found glycosylated)
• C terminal loops form phosphorylation and activation domains in cytosol
• Membrane passes arranged in a circular bundle

Question 23

The three components of the G-protein are:

Answer 23

• alpha subunit
• beta subunit
• gamma subunit

Question 24

Which subunit binds GTP? What does GTP do?

Answer 24

Alpha subunit - GTP activates G-protein

Question 25

An activated G-protein USUALLY dissociates into these 2 forms…

Answer 25

Alpha subunit.

Beta/gamma subunit remain associated.

Question 26

Describe the RGS proteins

Answer 26

Regulators of G-protein Signaling…function as GAPs

These are usually the target proteins which cause hydrolysis of GTP in alpha subunit and cause inactivation

Question 27

What is one caveat to the dissociation of G-proteins into two forms…

Answer 27

Some G-proteins are already associated with G- protein coupled receptor. GTP does not necessarily cause dissociation of the protein, but dissociation from the RECEPTOR

Question 28

What are the 3 families of trimeric G-proteins we have become familiar with…what does each do?

Answer 28

• Gs - activates adenylyl cyclase
• Gi - inhibits adenylyl cyclase
• Gq - activates phospholipase C-beta

Question 29

cAMP is a cyclic molecule that is derived from which molecule?

Answer 29

ATP

Question 30

How does cAMP affect protein kinase A?

Answer 30

Protein kinase A is held inactive by regulatory subunits. Binding of cAMP causes release of PKA

Question 31

Protein Kinase A phosphorylates these residues (amino acids). What is the general structural motif where this phosphorylation occurs?

Answer 31

• Serine/Threonine

- Arg - Arg - X - S/T - Y (hydrophobic)

Question 32

How does cAMP mediate a variety of responses?

Answer 32

cAMP is a mediator molecule in the pathway from a signaling molecule (hormone) attaching to a G-protein coupled receptor and inducing the desired effect through PKA

Question 33

What is CREB?

Answer 33

cAMP response element binding protein that is activated by PKA and induces cell transcription (it is a transcription factor)

Question 34

How does receptor desensitization occur?

Answer 34

Phosphorylation of C-terminal activating loops of GPCR through the kinase (GPCR kinase aka GRK) causes ARRESTIN to bind and inhibit G-protein signal transduction

Question 35

Describe how V. Cholera works to cause massive diarrhea taking in mind the the mechanism of cAMP and activation of these G-protein receptors

Answer 35

Vibrio cholera secretes exotoxin and enzyme - this enzymes catalyzes the ribosylation of Arg201 of G(alpha)S subunit. This prevents the hydrolysis of GTP to GDP by tuning off GTPase activity in the alpha subunit.

• Increase cAMP
• Increase PKA
• Activation of CFTR (ABC transporter)
• More efflux of Cl-, Na+, and H2O leads to diarrhea.