Cell Signalling

Question 1

What are the two types of cell-cell signalling?

Answer 1

1. direct interaction of a cell with other cells

2. action of diffusible signalling molecules over a distance

Question 2

What are the modes of signalling by secreted molecules?

Answer 2

Endocrine, paracrine, and autocrine

Question 3

What is the function of signalling molecules?

Answer 3

Transmit information between cells of multicellular organisms.

Question 4

How do signalling molecules transmit their information?

Answer 4

By binding to receptors on/in target cells.

Question 5

What are the 5 classes of ligands (signalling molecules) in animal cells?

Answer 5

1. steroid hormones (estrogen, glucocorticoids)
2. eicosanoids (prostaglandins)
3. neurotransmitters (acetylcholine, dopamine)
4. peptide hormones and polypeptide growth factors
5. simple gases

Question 6

What is the structure of steroid hormones? What are its modes of action? Where does it bind?

Answer 6

• small hydrophobic molecule, diffusible across cell membranes
• endocrine, paracrine, and autocrine modes of action
• bind to intracellular receptors (nuclear receptor superfamily)

Question 7

What is the structure of eicosanoids? What are its modes of action? Where does it bind?

Answer 7

• hydrophobic molecule synthesized from lipids in the plasma and nuclear membranes, are synthesized when needed and broken down rapidly
• paracrine or autocrine modes of action
• bind to cell surface receptors

Question 8

What is the structure of neurotransmitters? What are its modes of action? Where does it bind?

Answer 8

• hydrophilic molecules that do not cross the cell membrane
• endocrine, paracrine, and autocrine modes of action
• bind to cell surface receptors

Question 9

What is the structure of peptide hormones and polypeptide growth factors? What are its modes of action? Where does it bind?

Answer 9

• largest and most variable class, primarily hydrophilic and cannot cross the cell membrane
• endocrine, paracrine, and autocrine modes of action
• bind to cell surface receptors

Question 10

How do simple gasses move across the cell membrane? What are their modes of action? Where do they bind?

Answer 10

• move across the cell membrane via passive diffusion
• autocrine and paracrine modes of action
• bind directly to second messenger or enzymes (do not use receptors)

Question 11

What are receptors?

Answer 11

Proteins that undergo a conformational change when they interact with their ligand

Question 12

What does a change in conformation of receptors allow for? What does this initiate? What does it often involve?

Answer 12

• Allows the receptor to interact with other intracellular molecules
• initiates a cascade of reactions resulting in cell changes
• often involves modulation of transcription factors and changes in gene expression. May also involve modulation of enzymes or ion channels

Question 13

What ligands are associated with the nuclear receptor superfamily? What are their characteristics?

Answer 13

• ligands include glucocorticoids, steroid hormones, and thyroid hormones
• receptors are intracellular proteins (not associated with the membrane)
• these receptors are transcription factors, containing both a ligand binding domain and a DNA binding domain

Question 14

What is involved in glucocorticoid action? (6 steps)

Answer 14

1. glucocorticoid is inactive when bound to the Hsp90 chaperone
2. becomes active when bound to the ligand
3. two active receptors form a dimer
4. the dimer translocates to the nucleus
5. the dimer associates with the co-activator protein HAT
6. the resulting hormone complex binds to a specific DNA binding site and activates gene transcription

Question 15

How does gene regulation by the thyroid hormone receptor occur? (3 steps)

Answer 15

1. thyroid hormone receptor (dimer) is bound to DNA with or without the ligand
2. without the ligand, receptor binds the corepressor HDAC to repress gene transcription
3. when hormone is present, it binds the receptor and changes its conformation to dissociate from HDAC and associates with the coactivator HAT, allowing transcription

Question 16

What are the characteristics of G protein coupled receptors?

Answer 16

• largest family of cell surface receptors
• can bind to a variety of ligands including hormones, neurotransmitters, and peptides
• they are transmembrane proteins with multiple transmembrane domains

Question 17

What are the three subunits of heterotrimeric G proteins?

Answer 17

alpha, beta, and gamma

Question 18

What is the process of G protein regulation? (3 steps)

Answer 18

1. G protein is in inactive state. Hormone binding stimulates the release of GDP in exchange for GTP
2. G protein is in active state. The activated GTP-bound alpha subunit and beta-gamma complex dissociate from the receptor and interact with their targets
3. activity of the alpha subunit terminated by hydrolysis of the bound GTP. Inactive GDP-bound alpha subunit reassociates with the beta-gamma complex

Question 19

What are the characteristics of tyrosine kinase receptors?

Answer 19

they are cell surface receptors linked to intracellular enzymes and typically have one transmembrane domain

Question 20

Where can kinase enzyme activity reside?

Answer 20

either in the intracellular domain of the receptor itself or in a separate protein associated with the intracellular domain

Question 21

When do TK receptors dimerize? What does this activate?

Answer 21

• dimerize when bound to the ligand

- activates the receptors via phosphorylation of tyrosine residues on both the receptor itself and the target substrates

Question 22

What do phosphorylated tyrosine kinase receptors interact with?

Answer 22

Interact with proteins that contain an SH2 domain (downstream signalling molecules)

Question 23

What are nonreceptor tyrosine kinases associated with?

Answer 23

Associated with receptors that contain no catalytic activity

Question 24

What is intracellular signal transduction?

Answer 24

A chain of reactions that transmit chemical signals from the cell surface to their intracellular targets

Question 25

What is a second messenger? What is its function?

Answer 25

A compound that is modified as a result of a ligand-receptor interaction. Functions to relay the message from the receptor to the target

Question 26

What is adenylyl cyclase?

Answer 26

An enzyme that catalyzes the formation of cyclic AMP from ATP

Question 27

What is cAMP phosphdiesterase?

Answer 27

An enzyme that degrades cyclic AMP

Question 28

What does cAMP initiate?

Answer 28

Initiates intracellular transduction

Question 29

What does cAMP bind to?

Answer 29

a cAMP dependent protein kinase called protein kinase A (PKA)

Question 30

How does cAMP bind and activate PKA?

Answer 30

By causing dissociation of PKA subunits

Question 31

What can the intracellular signal received by a receptor be amplified by?

Answer 31

a single receptor activating multiple G proteins, resulting in 1 hormone molecule binding 1 receptor which can activate a large number of target proteins

Question 32

What are MAP pathways? What are they associated with?

Answer 32

• Mitogen-Activated Protein kinase pathways are transduction pathways that can be associated with both receptor and non-receptor tyrosine kinases.
• all consist of three kinases.

Question 33

What activates MAP kinases?

Answer 33

MAP kinases are activated in response to a variety of growth factors and other signalling molecules

Question 34

What is the Ras protein? What does it activate?

Answer 34

A peripheral lipid membrane anchored protein - not a kinase.
In the active GTP bound state, can interact with and activate Raf.

Question 35

What is the Raf kinase activated by? What does it activate?

Answer 35

Raf is activated by interacting with Ras.

Activates the MEK kinase by phosphorylation.

Question 36

What does the MEK kinase activate?

Answer 36

Activates members of the ERK family by phosphorylation

Question 37

What does the ERK kinase do?

Answer 37

Phosphorylates many target proteins, including other protein kinases and transcription factors.

Question 38

What are the steps in notch signalling? (3)

Answer 38

1. Notch receptor receives signal from Delta ligand on the surface of an adjacent cell
2. Ligand receptor binding activates gamma-secretase enzyme to cleave the intracellular domain of the notch
3. Notch intracellular domain translocates to the nucleus where it binds and activates transcription factors

Question 39

What is the activity of individual pathways regulated by?

Answer 39

feedback loops that control the extent and duration of signalling activity