Lecture 31 - Cell Signaling

Question 1

What are second messengers?

Answer 1

• intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules - first messengers

Question 2

What are the 3 (broad) ways signals can be transmitted?

Answer 2

1. cells are in direct contact
2. cells are close by
3. cells are far away

• endocrine
• autocrine
• paracrine

Question 3

What are the 4 types of receptors?

Answer 3

1. ligand-gated ion channel
2. G protein-coupled receptor (GPCR)
3. enzyme-coupled receptor (e.g., receptor tyrosine kinase)
4. nucelar receptor

Question 4

How do G protein-coupled receptors act?

Answer 4

via hydrolysis of GTP
G = guanine nucleotide binding

Question 5

Describe the activity of the GPCR and G protein

Answer 5

1. resting state: receptor not bound to ligand; G(alpha) is bound to GDP and associated with G(beta-gamma)
2. ligand binds receptor; receptor binds a G protein and acquires GTP
3. G protein subunits dissociate
4. G protein subunits activate or inhibit target proteins, initiating signal transduction events
5. G(alpha) subunit hydrolyzes its bound GTP to GDP, becoming inactive
6. subunits recombine to form an inactive G protein

Question 6

cAMP

Answer 6

• a second messenger of some G proteins
• G protein activates adenylyl cyclase, which makes cAMP
• cAMP activates PKA, a cAMP-dependent protein (kinase)

Question 7

How does cAMP activate PKA?

Answer 7

• cAMP binds to regulatory subunits and removes them
• protein kinase A phosphorylates many target proteins
• PKA activates/ inactivates different pathways (depending on cell type and proteins)

Question 8

Besides cAMP, what other second messengers do GPCRs use?

Answer 8

• IP3 and DAG
• a G protein activates phospholipase C (PLC)
• PLC cleaves PIP2 into DAG an IP3

Question 9

What does IP3 do?

Answer 9

• it activates Ca channels in ER membrane
  
  • IP3 receptors are ligand-gated ion channels

Question 10

What is another name for enzyme-coupled receptors?

Answer 10

protein kinase receptors

Question 11

How are enzyme-coupled receptors activated?

Answer 11

• these receptors are dimers => each dimer phosphorylates the other dimer, inducing a conformational change exposing the kinases

Question 12

What is an example of a tyrosine kinase receptor?

Answer 12

insulin receptor

Question 13

Steroid hormones

Answer 13

• a steroid that acts as a hormone
• steroids are lipids
• nuclear or cytoplasmic receptors

Question 14

Nuclear receptors often directly interact with _____

Answer 14

DNA

Question 14

What is an example of a nuclear receptor? What is the name of the hormone that binds this receptor?

Answer 14

• molting hormone receptor
• ecdysone = steroid hormone that controls insect molting