Block 3 - second messenger systems (L3-4)

Question 1

Cell-cell communication can occur via…

Answer 1

endocrine, paracrine, autocrine chemical messengers
direct transfer of factors via protein pores connecting the cytoplasm of neighboring cells

Question 2

Cell signaling can be initiated by…

Answer 2

• secretion of chemical messengers
• arrival of external signals (odorants, tastants, or xenobiotics)
• metabolites and ions

Question 3

The most common “molecular switch” is…

Answer 3

phosphorylation

Question 4

Specific kinases phosphorylate…

Answer 4

tyrosine, serine, and threonine amino acids

Question 5

What are kinases and phosphatases?

Answer 5

kinases - phosphorylate
phosphatases - dephosphorylate

Question 6

Phosphorylation can —– an enzyme’s catalytic activity

Answer 6

increase or decrease

Question 7

What are the 4 types of cellular receptors?

Answer 7

ligand gates ion channels
G protein couples receptors
catalytic receptors
nuclear receptors

Question 8

How do ligand gated ion channels work? What are 2 examples?

Answer 8

• integral membrane proteins interact with an ion channel to modify flux across the channel (the channel can be part of the receptor)
• ion acts as the initial second messenger

1. Nicotinic ACh receptors (muscles get signals from the nervous system to contract)
2. ATP-sensitive K+ channels (insulin secretion from pancreatic B cells)

Question 9

How do GPCRs work? What are 2 examples?

Answer 9

• activate a heterotrimeric complex G-protein (GTP-binding protein)
• modulates an enzyme or ion channel
• product of the enzymatic activity (or the ion) acts as the initial second messenger

1. a and B adrenergic receptors
2. glucagon receptors

Question 10

How do catalytic receptors work? What is an example?

Answer 10

• activate enzymatic activity of the receptor
  OR
• initiate a series of events that activate an enzymatic complex
• the initial second messenger is the product of the activated enzyme via phosphorylation of the substrate

1. insulin receptor

Question 11

How do nuclear receptors work?

Answer 11

• in the cytoplasm or nucleus
• act as transcription factors to modulate the transcription of specific genes
• alter protein expression of the gene products
• no second messengers

Question 12

What are the 6 steps to initiate a signaling event by a plasma membrane receptor?

Answer 12

1. recognition - ligand binds receptor
2. transduction - ligand binding induces conformational change, produces a second messenger
3. transmission - second messenger interacts with intracellular effectors
4. modulation of the effector - activates a protein kinase or phosphatase that changes the phos. state of a downstream target and alters its functionality
5. response - modified cellular function in highly specific ways
6. termination - feedback mechanisms stop the signaling events and return cellular function to a basal state

Question 13

What is amplification?

Answer 13

increased production of a second messenger at each step of a multi-step signaling cascade

leads to enhanced activation of a cellular process by several orders of magnitude

Question 14

What types of receptors transduce information from extracellular chemical messengers?

Answer 14

ligand gated ion channels
g protein couples receptors
catalytic receptors

Question 15

The ligand gated ion channels in skeletal muscle are called…

Answer 15

nicotinic acetylcholine receptors

Question 16

When a ligand binds a g protien-coupled receptor, what happens?

Answer 16

GDP is exchanged for GTP

G protein dissociates from the receptor and ligand releases

alpha subunit dissociates from By, so they can each interact with their appropriate effectors

GTP hydrolysis causes reassembly of the g protein

Question 17

G proteins can bind to 4 kinds of effectors:

Answer 17

• adenylate cyclases
• phosphodiesterases (PDEs)
• phospholipase C (PLC)
• Ca++ channels

Question 18

In what ways can G proteins interact with adenylate cyclase?

Answer 18

• Gs activates AC, increasing cAMP and increasing PKA activity
• Gi inactivates AC, lowering cAMP and decreasing PKA activity

Question 19

How can G proteins interact with phosphodiesterases (PDEs)?

Answer 19

• Gt activates PDE, breaks down cGMP, inactivating cGMP-dependent ion channels

Question 20

How can G proteins interact with phospholipase C (PLC)?

Answer 20

• Gq activates PLC, cleaves PIP2 into DAG and IP3
• DAG activates protein kinase C (PKC)
• IP3 stimulates Ca++ release from the ER

Question 21

What are the main types of catalytic receptors?

Answer 21

• receptor guanylate cyclases
• receptor serine threonine kinases
• receptor tyrosine kinases
• tyrosine kinase-associated receptors
• receptor tyrosine phosphatases

Question 22

What do receptor guanylate cyclases do?

Answer 22

produce cGMP from GTP (ex: ANP receptors)

Question 23

What do receptor serine-threonine kinases do?

Answer 23

phosphorylate serine and threonine (ex: TGF-B receptors)

Question 24

What do receptor tyrosine kinases do?

Answer 24

phosphorylate tyrosine (ex: NGF receptors)

Question 25

What do tyrosine kinase-associated receptors do?

Answer 25

interact with and activate cytosolic tyrosine kinases (ex: growth hormone receptors)

Question 26

What do receptor tyrosine phosphatases do?

Answer 26

dephosphorylate tyrosine (ex: CD45)

Question 27

The insulin receptor is a type of…

Answer 27

catalytic receptor, specifically a tyrosine kinase receptor

Question 28

Describe the mechanism for a tyrosine kinase receptor in 5 steps

Answer 28

1. binding: single exofacial subunit binds ligand, causing dimerization of two receptors (insulin is pre-dimerized)
2. activation: conformational change causes auto-phosphorylation of tyrosine residues and activation of the receptor complex, which further increases in receptor tyrosine kinase activity
3. enhancing: enhanced tyrosine phosphorylation of cytosolic proteins
4. effector modification: activation of downstream effectors modifies cell function
5. termination: receptor activity ceases when 1) ligand receptor complex is internalized or 2) the action of a specific phosphatase dephosphorylates the receptor