Exam 2 Lecture 10

Question 1

What is signal transduction?

Answer 1

Cell to cell communication

Question 2

What is the process of signal transduction?

Answer 2

1. Cells receive external signals through receptor molecule (sender cell)
2. Signal is converted into another chemical form or is transduced
3. Transduction is often amplified and is regulated by intracellular signaling proteins
4. A cellular response is created

Question 3

What are the different cell responses?

Answer 3

1. gene expression
2. membrane transport
3. metabolism
4. cell growth/death

Question 4

What is the overall idea of signal transduction?

Answer 4

Information from the environment that gets transmitted inside a cell generates a cellular response

Question 5

What is the purpose of signal transduction?

Answer 5

1. coordinate cell metabolism, growth, and development
2. ensure homeostasis among tissues and organs
3. response to external stimuli like light, pressure, and heat

Question 6

What is a signal transduction cascade?

Answer 6

Sequential biochemical events that transfer a signal through a series of reactions that activate intermediate molecules and to the final target

Question 7

What are the three main steps in a signal transduction cascade?

Answer 7

1. reception
2. transduction
3. response

Question 8

What is signal amplification?

Answer 8

One signaling molecule on the outside can activate downstream signaling molecules over and over again to create a huge cascade on the inside of the cell and amplify the signal

Question 9

How do metabolic pathways differ from signaling pathways?

Answer 9

1. Series of enzymatic reactions (in which the product of one reaction is the substrate of the next reaction) to convert a metabolite into one or two other metabolites to synthesize or degrade biomolecules
2. Can include the transportation of a metabolite from one compartment of the cell to another or even across the plasma membrane
3. Regulated depending on the needs of the cell and substrate availability

Question 10

How do signaling pathways differ from metabolic pathways?

Answer 10

1. Have external ligands that trigger intracellular events
2. Involves the enzymatic modification of a protein (post translational) to alter its conformation, intermolecular interactions, cellular locations, and/or its function
3. Involves the regulation of gene expression and changes in protein activity

Question 11

What are the 5 different modes of cell-cell communication?

Answer 11

1. Juxtacrine
2. Paracrine
3. Endocrine
4. Synaptic/neuronal
5. Autocrine

Question 12

What is juxtacrine signaling?

Answer 12

Is direct cell to cell contact in which two surface proteins bind

Question 13

What is endocrine signaling?

Answer 13

Involves hormones that get secreted into the bloodstream so has no cell-cell contact, has a low concentration (10^-12 to 10^-9 M), and has a high affinity receptor (has to find their target), response can take minutes to hours

Question 14

What is paracrine signaling?

Answer 14

Involves the sender and target cell being nearby one another in which the secreted ligands target nearby cells, has a high local concentration (10^-9 to 10^-6 M), has a low affinity receptor, response is rapid and transient within seconds to minutes

Question 15

What is the relationship between the affinity of the receptor and the concentration?

Answer 15

Direct relationship in which low concentration = high affinity receptor and high concentration = low affinity receptor

Question 16

What is synaptic/neuronal signaling?

Answer 16

Involves the pre-synaptic neuron and the post-synaptic neuron/target cell (which has the receptor) and the synapse between the neuron and target cell is very short distance, has a very high local concentration (10^-6 to 10^-3 M), has a low affinity receptor that dissociates rapidly in milliseconds (has a short life)

Question 17

Synaptic/neuronal signaling is a special type of what kind of signaling?

Answer 17

Paracrine signaling

Question 18

What is autocrine signaling?

Answer 18

The sender and target cell are the same cell (cell is telling itself so there are receptors on itself) and the response time is similar to paracrine signaling which is rapid and transient from seconds to minutes

Question 19

What are secreted molecules for receptors?

Answer 19

They are first messengers and ligands that can be a variety of molecules ranging in size and chemical types

Question 20

What are some examples of large ligands?

Answer 20

Proteins and polypeptides

Question 21

What are some examples of small ligands?

Answer 21

Amino acids, lipids, and nucleotides

Question 22

What are some examples of other chemical types of ligands?

Answer 22

Steroids, vitamins, histamine, and modified amino acids

Question 23

What are some examples of receptors?

Answer 23

Intracellular proteins and integral membrane proteins

Question 24

How does the intracellular receptor for steroid hormones, thyroid hormones, and vitamins work?

Answer 24

Hormones are lipid soluble (hydrophobic) so they can diffuse through the membrane and bind to the intracellular receptor → signal gets propagated by changes in the receptor upon binding which can lead to altered gene expression

Question 25

What is an example of an intracellular receptor?

Answer 25

Hormonal nuclear receptor in which the hormonal response element is highly specific to the given hormone/nuclear receptor

Question 26

What is another example of an intracellular receptor?

Answer 26

Thyroid nuclear receptor

Question 27

What is the mechanism of the thyroid nuclear receptor?

Answer 27

1. Thyroid hormone is lipid soluble so it can diffuse through the plasma membrane 2. Once inside the cell, the thyroid hormone can bind to the receptor and promote the dimerization of the receptor 3. Coregulatory proteins are recruited 4. Promotes DNA binding and specific recognition of thyroid response element (TRE) → affects signaling outcome on transcription

Question 28

Where does the thyroid hormone bind?

Answer 28

It binds in the middle of one of the dimers of the ligand binding domain

Question 29

What are the 4 major cell-surface receptors?

Answer 29

1. ligand gated ion channel receptors 2. enzyme-linked or catalytic receptors 3. cytokine family receptors 4. G-protein coupled receptors (GPCR)

Question 30

What are the 3 types of effects of first messenger binding?

Answer 30

1. generation of second messengers 2. change in the plasma membrane potential 3. activation of effector-enzyme cascades by direct interaction of receptor or through coupling/transducing proteins

Question 31

What is a second messenger and what does it do?

Answer 31

They are typically small, intracellular molecules that transmit and amplify the initial signal from extracellular first messenger binding to receptors

Question 32

What are some examples of second messengers?

Answer 32

They can be inorganic ions such as Ca2+ or organic products of enzyme catalyzed reactions

Question 33

What are some examples of water soluble second messengers?

Answer 33

cAMP, cGMP, and inositol triphosphate (IP3)

Question 34

What are some examples of lipid soluble second messengers?

Answer 34

diacylglycerol (DAG) and PIP3

Question 35

What does downstream signaling control do?

Answer 35

It's a mechanism to control protein-protein interactions and enzymatic activity

Question 36

What does phosphorylation of a protein do?

Answer 36

1. It can induce a conformational change like catalytic activity that results in an altered function 2. It can promote protein-protein interaction in which the phosphorylated residue in the binding site is recognized by a binding partner but the unphosphorylated one is not

Question 37

What enzymes are needed for phosphorylation?

Answer 37

Kinases will phosphorylate a protein using ATP and a phosphatase will remove a phosphate group and dephosphorylate the protein

Question 38

What is a scaffold and what is its importance?

Answer 38

They are large assemblies of proteins that form under the control of phosphorylation and can relay a message much faster than waiting for a protein to float by and relay the message

Question 39

What is another example of a downstream signaling control?

Answer 39

GTP binding regulatory proteins (GTPases)

Question 40

What do G proteins do?

Answer 40

They bind and hydrolyze GTP and the GDP bound form has a different conformation than the GTP bound form

Question 41

The exchange of GDP for GTP is catalyzed by what enzymes?

Answer 41

Guanine nucleotide exchange factors (GEFs) → can be coupled to GPCR and GPCRs can act as GEFs

Question 42

If GTP is bound

Answer 42

Signal is turned ON

Question 43

If GDP is bound

Answer 43

Signal is turned OFF (hydrolysis turns off the signal)

Question 44

Ras proteins are

Answer 44

1. not trimeric 2. small GTPase/monomeric G-protein that functions in cell proliferation and protein synthesis 3. bad things happen when it has mutations because it could become oncogenic 4. Small and soluble

Question 45

How are cell surface receptors turned off to terminate signaling?

Answer 45

1. Rapidly reduce the level of the message/agonist availability in the extracellular vicinity of the target cell (common for synaptic signaling) 2. Receptor loss/desensitization

Question 46

How can you reduce the level of message to terminate signaling?

Answer 46

1. Rapid re-uptake of neurotransmitters by transporters (like serotonin, dopamine, SERT!) 2. Breakdown by enzymes (acetylcholine esterase)

Question 47

How can receptor loss or desensitization occur?

Answer 47

1. Reduced receptor availability by internalization (endocytosed) or degradation of the agonist bound receptor complex 2. Functionally adapted by modifying receptors to be less sensitive (by phosphorylation or dephosphorylation)