Term 1- Lec 7&8- Signal Transduction

Question 1

The 4 categories of cell signaling

Answer 1

Autocrine, Paracrine, Endocrine, and Neuronal

Question 2

Autocrine signaling

Answer 2

Short distance signaling that is meant for cells that are the same as the signaling cell. (Local distribution of ligand among cell population)

Question 3

Paracrine signaling

Answer 3

Short distance signaling that is meant for different types of cells from the signaling cell. (Local distribution of ligand among cell population)

Question 4

Endocrine signaling

Answer 4

Long distance signaling. Utilizes bloodstream to transport ligands long distances.

Question 5

Contact-dependent signaling

Answer 5

Cells have a ligand attached to the surface which is mirrored by receptors on the target cells.

Question 6

This signaling limits growth

Answer 6

Contact dependent signaling. This feature is often lost in cancer cells.

Question 7

Type I Diabetes

Answer 7

Autoimmune. Insulin-producing (ß-pancreatic) cells are exhausted because signal is never received and the cells continue to produce the signal until they cannot anymore/told to quit forever

Question 8

Type II Diabetes

Answer 8

Insulin is made, but target cells become less responsive. Insulin resistance.

Question 9

Neuronal signaling

Answer 9

Specialized type of Paracrine signaling. Nerve to non-neuronal target cell. Signaling not meant for many cells and is often only delivered to one.

Question 10

Long and short distance nerve signal travel occur where respectively?

Answer 10

Nerve signals travel long distances in axons and short distances across synapse.

Question 11

The two phases of neuronal signaling

Answer 11

1. Through the neuron via electric potential.

2. Signal to the target cell via neurotransmitters across synapse. (ie Acetylcholine)

Question 12

Two mechanisms for Ligand Induced Signaling in cells

Answer 12

1. Diffusion across the plasma membrane to activate intracellular receptors. (i.e. Steroid hormones)
2. Binding and activation of cell surface receptors. (i.e. Insulin)

Question 13

How do steroid hormones travel in the blood stream?

Answer 13

They require a transport protein because they are hydrophobic and not soluble.

Question 14

What are the names of the 5 steroid hormones

Answer 14

1. Testosterone
2. Estradiol
3. Progesterone
4. Cortisol
5. Aldosterone

Question 15

In what type of cell and how is Nitric Oxide synthesized?

Answer 15

Arginine is acted on by Nitric Oxide Synthase (eNOS) in the endothelium to make NO

Question 16

Why can NO only affect it’s surrounding cells?

Answer 16

It has a very short half-life, thus it cannot make it that far.

Question 17

What is the purpose of NO?

Answer 17

To cause vasodilation

Question 18

What are the three cell types involved in NO signaling

Answer 18

Nerve terminal, Endothelial cell, and Smooth m. (surrounding the endothelial cell of the blood vessel)

Question 19

What is nitroglycerin’s role in vasodialtion?

Answer 19

Undergoes chemical conversion into NO, causing dialtion of the blod vessels in the heart.

Question 20

The two types of transmembrane receptors extracellular ligands bind

Answer 20

1. G-protein coupled receptor (GPCR)

2. Receptor tyrosine kinase (RTK)

Question 21

Ligand binding of GPCR/RTK initiates

Answer 21

Phosphorylation cascades

Question 22

Phosphate group transfer is what type of modification?

Answer 22

Covalent modification

Question 23

This type of enzyme forms new phophate bonds

Answer 23

Kinases

Question 24

This type of enzyme breaks phophate bonds

Answer 24

Phosphotases

Question 25

Kinase proteins transfer phosphates to what functional groups on which AAs?

Answer 25

The hydroxyl of Serine, Threonine, Tyrosine

Question 26

Where do kinases transfer the phosphate FROM?

Answer 26

The terminal phosphate of ATP

Question 27

The 4 targets of Kinases

Answer 27

1. Other kinases 2. Phosphatases 3. Metabolic enzymes 4. Transcription factors

Question 28

The two types of ligands that GPCR and RTK bind are:

Answer 28

1. Encoded by genes | 2. Produced through a series of enzymatic rxns

Question 29

Most growth factor bind to:

Answer 29

Receptor Tyrosine Kinase

Question 30

Molecules that activate their receptor

Answer 30

Agonists

Question 31

Molecules that interfere with receptor activation by it's natural ligand

Answer 31

Antagonists

Question 32

Epinephrine and Glucagon both bind to what type of receptor. What do they affect?

Answer 32

GPCRs. They alter metabolism in the cell

Question 33

G∂-s

Answer 33

Activates Adenylate Cyclase

Question 34

G∂-i

Answer 34

Inhibits Adenylate Cyclase

Question 35

G∂-q

Answer 35

Activates Phospholipas C

Question 36

Adrenergic receptors

Answer 36

Bind to specific ligands to regulate metabolic processes

Question 37

The 3 main classes of adrenergic receptors

Answer 37

∂1, ∂2, and ß

Question 38

What is a ß subunits activity dependent on?

Answer 38

The G∂ proetin it is bound to.

Question 39

Cholera toxin ribosylates (adds ADP-ribose) what? What happens?

Answer 39

G∂-s. G∂-s cannot hydrolyze GTP, Adenylate cyclase remains active, cAMP continues to be produced

Question 40

Pertussis toxin ribosylates (adds ADP-ribose) what? What happens?

Answer 40

G∂-i. G∂-i cannot get rid of GDP, Adenylate cyclase activity cannot be produced, cAMP continues to be produced.

Question 41

cAMP increases the activity of

Answer 41

Protein Kinase A (PKA)

Question 42

What is the structure of PKA?

Answer 42

2 regulatory subunits and 2 catalytic subunits

Question 43

How does cAMP activate PKA?

Answer 43

cAMP binds to the regulatory subunits, which release the catalytic units

Question 44

What can PKA phosphorylate

Answer 44

It can phosphorylate the transcription factor for CREB (cAMP regulatory element binding protein) to regulate gene expression

Question 45

What enzyme deactivates cAMP, and how?

Answer 45

cAMP Phosphodiesterase. Unbinds the phosphate that makes it cyclic, turning it into low energy AMP

Question 46

The naming difference between the two types of GPCR pathways

Answer 46

G∂-s: activates Adenylate Cyclase | G∂-q: activates Phopholipase C

Question 47

What cleaves PIP2, and what is produced?

Answer 47

PIP2 is cleaved by PLC to create DAG (stays in membrane) and IP3.

Question 48

Role of Ca2+ in PLC pathway

Answer 48

Ca2+ acts as a second messenger. It is released via the IP3 signal, then it binds with PKC to activate it (PKC later connects to DAG at the membrane)

Question 49

How are cytoplasmic Ca2+ levels lowered?

Answer 49

Ca-ATPase in the ER membrane uses active transport to pump Ca2+ back intot he ER. This shuts down Ca2+ dependent signaling

Question 50

Calmodulin

Answer 50

Activated when bound to Ca2+. causes conformational changes in other proteins by "squeezing" them. Lacks enzymatic properties

Question 51

Calmodulin activates

Answer 51

CaM Kinase II.

Question 52

CaM Kinase activation cycle

Answer 52

* Ca/Calmodulin wrap inactive CaM Kinase !! to activate it. * CaM Kinase II autophosphorylates * Once Ca levels drop, calmodulin becoves inavtive and unwraps from CaM Kinase II. * Phosphate attached to CaM Kinase II keeps the kinase ~50-80% active.

Question 53

General structure of RTK's

Answer 53

Extracellular ligand binding site and Intracellular Tyrosine Kinase Domain

Question 54

Ras is what type of enzyme?

Answer 54

GTPase

Question 55

Where is Ras found in the cell?

Answer 55

Ras is anchored to the plasma membrane by a covalently attached lipid tail

Question 56

What stimulates Ras activity?

Answer 56

Guanine exchange factor (GEF) INFLUENCE (doesn't do the work) GTP binding to Ras

Question 57

What down regulates Ras?

Answer 57

GTPase activating proteins (GAP) INFLUENCE (doesn't do the work) the hydrolysis of GTP on Ras

Question 58

What type of protein is SOS and what recruits it to the membrane

Answer 58

SOS is a GEF. GRB2 recruits SOS so that it can activate Ras.

Question 59

Enzyme that catalyzes cAMP to AMP

Answer 59

cAMP Phosphodiesterase