Cell Signalling

Front 1

How many receptors does a human genome code?

Back 1

Estimated at 1500

Front 2

What 3 things does the growth and survival of a cell in a multicellular organism depend on?

Back 2

1. Intercellular communication

2. Monitoring of the environment

3. Formation of appropriate stimuli responses

Front 3

What is the first basic principle of cell signalling?

Back 3

Cells can only respond to a signalling molecule if they posses a receptor for that specific signalling molecule

Front 4

What are the 6 types of cell signalling?

Back 4

1. Endocrine

2. Paracrine

3. Autocrine

4. Neuronal

5. Contact-Dependent

6. Direct

Front 5

What 2 types of cell signalling uses molecules produced at VERY LOW CONCENTRATIONS?

Back 5

Paracrine and autocrine

Front 6

What kind of cell signalling uses hormones? are they produced at high or low concentrations?

Back 6

The endocrine signalling uses hormones, which are produced at high concentrations

Front 7

Does the endocrine communication mechanism affect cells at a short or far distance?

Back 7

As they are produced at high concentrations, they can circulate the body and therefore affect cells at a greater distance

Front 8

What type of signalling molecules are used in the paracrine communication mechanism? Are they produced at low or high concentrations? Do they affect near of faraway cells?

Back 8

Paracrine signalling molecules are "local mediators", which are produced at VERY LOW CONCENTRATIONS, and therefore only affect cells near the original signal cell

Front 9

Autocrine and paracrine are very similar, however express one significant difference. What is it, and in what type of cells is autocrine normally seen in because of it?

Back 9

While autocrine also uses "local mediators", which are created at very low concentrations, the signal cell has receptors for those local mediators and therefore is self-stimulating. This is often seen in cancer cells.

Front 10

What is the signalling molecules in neuronal signalling? Do they act at a short or long distance?

Back 10

Neuronal signalling use neurotransmitters as their signalling molecules, which act at short distances (i.e. across a synaptic cleft)

Front 11

Contact-dependent signalling need contact between what two units in order to occur?

Back 11

Contact between a cell surface signalling molecule of the signalling and a receptor on the surface of the target cell.

Front 12

How does direct signalling work? Neighbouring cells are connected by what (2 options)?

Back 12

Direct signalling is the flow of molecular traffic between neighbouring cells. These are connected by gap junctions or plasmodesmata

Front 13

What is used to classify signalling systems?

Back 13

The distance that signals must travel.

Front 14

True or False: Receptors can only be on the outside of the cell

Back 14

False! Receptors can be inside or outside.

Front 15

What is cortisol? Where is it produced and why? What does cortisol production result in (2)?

Back 15

Cortisol is a steroid hormone. It is produced in the adrenal cortex in response to stress. Cortisol production causes an increase in blood pressure and blood sugar

Front 16

How do cell surface receptors transmit signals?

Back 16

Binding signals do not enter the cell; instead, the signal is transmitted from the receptor to a small molecule in the cell.

Front 17

What are some examples of intracellular signalling molecules? (there are 3)

Back 17

1. cAMP

2. Ca2+

3. cGMP

Front 18

What are the 4 types of cell surface receptors?

Back 18

1. Ion-Channel-Coupled Receptors (ICC)

2. G-Protein-Coupled Receptors (GPC)

3. Enzyme-Coupled Receptors (ECs)

3a. Receptor linked to an enzyme

3b. Receptor associated with an enzyme

Front 19

What kind of signalling occurs with ion-channel-coupled receptors?

Back 19

Rapid signalling between nerve cells and other electrically excitable cells.

Front 20

Give an example of ion-channel-coupled receptors

Back 20

Neurotransmitter gated ion channel

Front 21

what are G-Protein-Coupled Receptors mediated by?

Back 21

Mediated by Heteretrimeric GTP-Binding Protein

Front 22

What are the targets of G-Protein-Coupled Receptors?

Back 22

GPC Receptors target plasma membrane-bound proteins, which are either enzymes or ion channels

Front 23

Give an example of a G-Protein-Coupled Receptor (there are 2 named in lecture)

Back 23

Rhodopsin or Transducin

Front 24

Receptors linked to enzymes have enzymatic activity in which part of their body?

Back 24

In the cytoplasmic tail

Front 25

Give an example of a receptor linked to an enzyme

Back 25

Receptor Tyrosine Kinase (RTK)

Front 26

What is a receptor associated with an enzyme?

Back 26

a Cytokine receptor

Front 27

What are four ways that a cell can respond to signals?

Back 27

1. Survive

2. Grow and Divide

3. Differentiate

4. Die

Front 28

What are the two major signalling mediators?

Back 28

1. Signalling via phosphorylation

2. Signalling via GTP-Binding

Front 29

What is the main difference between signalling via phosphorylation and signalling via GTP-binding?

Back 29

Signalling via phosphorylation uses ATP and ADP to turn the signal on, while signalling via GTP uses GDP and GTP to turn the signal on

Front 30

What is a cognate receptor?

Back 30

Receptors that will bind to a ligand

Front 31

What kind of bond occurs between the ligand and its receptors?

Back 31

Noncovalent bonds

Front 32

What is the specificity reaction equation? (hint: looks like a chemical equilibrium reaction)

Back 32

R+L <--> RL

Front 33

What does the dissociate constant represent? What is the equation to calculate the dissociate constant?

Back 33

The dissociate constant (Kd) represents affinity. Its equation is:

Kd = [R][L]/[RL]

Front 34

What are three ways in which signals can be integrated?

Back 34

1. One receptor can activate multiple pathways

2. More than one receptor can activate the same pathway

3. Receptors activate separate pathways, but the pathways affect each other

Front 35

Integration plays an important role in what?

Back 35

Regulation

Front 36

What will signalling pathways often have several of?

Back 36

Amplification steps

Front 37

What 2 people were awarded the nobel prize in physiology or medicine in 1994 for discovering G-proteins?

Back 37

Alfred Gilman and Martin Rodbell

Front 38

How many G-Protein Couples Receptors (GPCRs) are there in the human genome?

Back 38

More than 800

Front 39

Around 40-50% of all drugs target what?

Back 39

Almost half of all drugs target GPCR activity

Front 40

How many transmembrane spanning regions are there in GPCRs?

Back 40

7

Front 41

What happens when an α subunit is bound to GDP?

Back 41

It associates with the βγ (G-Beta Gamma Complex) subunit and renders it inactive

Front 42

What are the two types of G-Proteins?

Back 42

1. Monomeric

2. Heterotrymeric

Front 43

What is the mechanism for GPCR activation?

Back 43

Ligand binds to the receptor--> receptor binds to a G-Protein--> Gα releases GDP and binds with GTP--> Gα and Gβγ subunits separate--> Subunits either activate or inhibit target proteins, which initiates signal transduction events-->Gα subunit hydrolyzes attached GTP to GDP, deactivating it-->Subunits recombine to make an inactive G protein, restarting the process

Front 44

What secondary messenger causes "flight or fight" response? How does it do so?

Back 44

cyclic Adenosine MonoPhosphate (cAMP) activates Protein Kinase A (PKA), which primes muscles for quick action

Front 45

What do V. cholerae adhere to? What do they secrete following adhering?

Back 45

They adhere to intestinal cells, and secrete choleragen (an AB exotoxin)

Front 46

How does cholera unfold (the steps)?

Back 46

V.Cholerae adhere to intestinal cells--> secrete choleragen--> A subunit enters intestinal epithelial cells and activated adenylate cyclase via ADP-ribosylation-->water and chloride are hyper-secreted from cells

Front 47

What is PKA activated by?

Back 47

cyclic Adenosine MonoPhosphate (cAMP)

Front 48

What is PKA's regulatory affinity (Kd)? What is its catalytic affinity?

Back 48

49 kd regulatory

38 kd catalytic

Front 49

What are the 2 lobes in the PKA catalytic subunit?

Back 49

The N-lobe and the C-lobe

Front 50

What occurs during S binding in term of PKA catalytic subunits?

Back 50

The N and C lobes move closer together

Front 51

PKA can regulate what?

Back 51

Gene expression?

Front 52

What do CRE, CREB, and CBP each do?

Back 52

Camp Response Elements (CRE) - catalyzes site-specific recombination of DNA

Camp Response Element-Binding Proteins (CREB) - increases or decreases transcription of genes

CREB Binding Protein (CBP) - activates transcription

Front 53

What are inositol-1,4,5-triphosphatase (IP3) and diacylglycerol (DG)? What are they the breakdown products of? What is this breakdown initiated by?

Back 53

IP3 and DG are secondary messengers formed from the breakdown of phasphatidlyinositol-4,5-biphosphate (PIP2), which is initiated by phospholipase C (PLC)

Front 54

How is PLC activated?

Back 54

Receptor-ligand complex associates with Gα-->GDP is replaced by GTP on the Gα--> Gα and Gβγ subunits dissociate-->GTP-Gα complex binds to Phospholipase C--> PLC is activated, causing cleavage of PIP2 into IP3 and DAG--> IP3 is released into cytosol, triggering calcium release--> remaining DAG in cytosol activates protein kinase C

Front 55

Is calcium concentration in the cytosol high or low?

Back 55

Very low

Front 56

What is calmodulin?

`

Back 56

A highly conserve polypeptide with four high Ca2+ sites

Front 57

What activates receptor tyrosine kinases?

Back 57

Trans-autophosphorylation

Front 58

What is the GEF for Ras?

Back 58

Sos (son of Sevenless)

Front 59

What are mitogens?

Back 59

Growth/proliferation signals

Front 60

What are the three components to mitogen activated proteins (MAPs)?

Back 60

1. MAP kinase (MAPK)

2. MAP kinase kinase (MAPKK)

3. MAP kinase kinase kinase (MAPKKK)

Front 61

Mammalian cells have how many of each of the three MAP component genes?

Back 61

12 MAPK, 7 MAPKK, and 7 MAPKKK

Front 62

What is BMP? What does it do?

Back 62

Bone Morphogenic Protein form bone and cartilage`

Front 63

What is R-Smad?

Back 63

Receptor Smads that are phosphorylated on their c-terminus

Front 64

What is I-Smad?

Back 64

Inhibitor Smad prevents the phosphorylation of Receptor Smads

Front 65

What is C-Smad?

Back 65

Co-Smads interact with R-smads during signalling`

Front 66

What pathway do bacteria, yeasts, and plants use, but not humans?

Back 66

Histidine-Kinase-Associated Receptors (HKA)

Front 67

What do HKA receptors mediate?

Back 67

Bacterial chemotaxis