Lecture 2- Signal Transduction

Question 1

Describe Endocrine signaling

Answer 1

Chemical signal between cells that are far apart (signal travels through the bloodstream)

Question 2

Describe Paracrine signaling

Answer 2

Chemical signal between cells neighboring in the same tissue (close)

Question 3

Describe Autocrine signaling

Answer 3

Chemical signaling by a cell to itself

Question 4

What are the mechanisms that facilitate paracrine and autocrine signals limiting their diffusion so that they are delivered to their proper target?

Answer 4

• Rapid endocytosis of signal by neighboring cells
• Destruction by extracellular enzymes
• Immobilization by extracellular matrix

Question 5

In an axon terminal, at the synapse, when Na+ is released, is this an example of depolarization or hyperpolarization?

Answer 5

depolarization

Question 6

What is the term for a signal molecule and what does it bind to at its destination?

Answer 6

It is called a ligand and it binds to a receptor (can be protein, lipoprotein, nuclear receptor inside the cell, or ion channels)

Question 7

What are receptors associated with (think when ligand binds to it)?

Answer 7

Effector molecules

-(enzymes, channels, transport proteins, contractile elements, transcription factors…)

Question 8

What are the 4 main types of receptors that we are focused on?

Answer 8

• Ligand-gated ion channel receptors (simplest)
• G protein-coupled (largest group)
• Catalytic receptors
• Nuclear receptors

Question 9

What are the key features of a ligand-gated ion channel receptor?

Answer 9

• integral membrane proteins
• hybrid receptor/channels
• involved in signaling between electrically excitable cells

Question 10

In ligand-gated ion channels, what are the receptors called?

Answer 10

Ionotropic receptors

Question 11

What are the key features of G protein-coupled receptors?

Answer 11

• Integral plasma membrane proteins

- Work through an intermediary (the intermediary is a GTP-binding complex called a G protein)

Question 12

What are the components of G protein-coupled receptors (GPCRs)?

Answer 12

• Seven membrane-spanning alpha-helical segments
• An extracellular N terminus that is glycosylated
• Large cytoplasmic loop composed mainly of hydrophilic AAs between helices 5 and 6
• A hydrophilic domain at the cytoplasmic C terminus

Question 13

T/F. G proteins are heterotrimers.

Answer 13

True

Question 14

When is a G protein active?

Answer 14

When it hydrolyzes GTP and binds GTP (inactive when GDP is bound)

Question 15

What are the three subunits that compose a G protein?

Answer 15

Alpha, Beta, Gamma

Question 16

What does the alpha subunit of G protein do?

Answer 16

binds and hydrolyzes GTP

Question 17

What does the Beta-Gamma subunit complex of a G protein do?

Answer 17

Anchors the trimeric complex to the membrane (also functions in signal transduction by interacting with certain effector molecules)

Question 18

What are the steps of the G protein activation cycle

Answer 18

1. a ligand binds to the GPCR which then interacts with the G protein to promote a conformational change to release GDP and bind GTP
2. The GDP to GTP stimulates dissociation of the complex from the receptor
3. Results in free alpha subunit and Beta-gamma complex
4. a-complex now interacts in plane of membrane with downstream effectors (ex. adenylyl cyclase, phospholipases)- βγ-subunit can now activate ion channels or other effectors
5. the a-subunit terminates the signaling by hydrolyzing GTP to GDP and Pi, then rejoins to original position as heterotrimer

Question 19

What is the role of 2nd messengers?

Answer 19

to amplify a signal

Question 20

T/F. Second messengers are generally cell specific and can produce different effects in different cells.

Answer 20

True

Question 21

what does Adenylyl cyclase do?

Answer 21

Converts ATP to cAMP (makes cyclic compounds)

Question 22

What converts ATP to cAMP?

Answer 22

Adenylyl cyclase

Question 23

What does Phosphodiesterase do?

Answer 23

Converts cGMP to GMP (breaks cyclic compounds)

Question 24

What converts cGMP to GMP?

Answer 24

Phosphodiesterase

Question 25

What reaction does Phospholipase do (ex. Phospholipase C)?

Answer 25

Converts PIP2 to DAG + IP3
(Phosphatidyllinositol bisphosphate
Diacyglycerol
Inositol Triphosphate)

Question 26

What converts PIP2 to DAG + IP3?

Answer 26

Phospholipase

Question 27

What residues does phosphokinase A (PKA) transfer a phosphate group to?

Answer 27

Serine

Threonine

Question 28

What does IP3 activate?

Answer 28

Signals the release of Ca from the ER (can travel through cytosol)

Question 29

What does DAG activate?

Answer 29

Activates Protein Kinase C (PKC) (stays in the plane of membrane) (PKC goes to membrane because of Ca release)

Question 30

Example: What are the products if phosphatidylcholine are broken down via PLC and PLD, respectively?

Answer 30

PLC leads to DAG (cuts off/before phosphate group)

PLD leads to phosphatidic acid (cuts after phosphate group, cutting only choline off)

Question 31

what is the most important function of DAG?

Answer 31

to activate protein kinase C (PKC)

Question 32

What does PKC require for activation?

Answer 32

Both DAG and Ca

Question 33

How is Ca’s signal transmitted via the cell?

Answer 33

4 Ca bind to Calmodulin (CaM), which allows it to bind to other proteins; (like binding and activating protein kinases- CaM kinases)

Question 34

What is an example of an important CaM kinase in smooth muscle cells?

Answer 34

Myosin Light Chain Kinase (MLCK)