Lecture 24

Question 1

Describe signal transduction characteristics (describe it, receptors, intracellular signaling proteins, effector proteins)

Answer 1

it occurs as cell to cell communication that MUST traverse from outside of the cell, to the inside of the cell

Receptors are what serve to move the signal from the “signal molecule” to the inside of the cell

intracellular signaling proteins carry the message from the receptor to the intracellular target

Effector proteins conduct whatever the signal was demanding

Question 2

Name the 5 ways to stop (desensitize) a signal in a signal transduction pathway

Answer 2

receptor sequestration via endosome formation

Receptor destruction by endosomes (that contain the receptors) fuzing with lysosomes

A decrease in hormone levels (decreased adenylyl cyclase means less cAMP and PKA activity as well)

Removing the signal molecule (phosphodiesterases will remove a cAMP

GRK’s and arrestin

Question 3

Name the 5 types of cell signaling

Answer 3

Endocrine Sig: distance

Paracrine Sig: distance

Synaptic Sig.

Autocrine sig: what cells it affects

Direct Sig.

Question 4

during signal transduction, external signal induce what 2 types of responses? describe both of them.

Answer 4

(Fast response) change in activity or function of enzymes or proteins in the cell

(slow response) change in amounts of proteins by change in expression of genes

Question 5

what are the 3 things that “effector proteins” usually conduct, upon receiving instruction from an intracellular signaling protein?

Answer 5

Altered metabolism

Altered gene expression

Altered cell shape or movement

Question 6

What happens if you knockout the “leptin” gene?

Answer 6

(leptos means thin)

Leptin is released from fat cells and signals the hypothalamus that you are full

when this doesn’t happen, you wont feel full and will gain weight

Question 7

Describe Endocrine Signaling

Answer 7

long distance signaling that travels through the bloodstream to it’s target tissue(s)

freely diffusible signals

long lasting half life (must survive the “trip” in the blood stream)

Question 8

Describe Paracrine Signaling

Answer 8

acts locally to affect nearby cells

short lived signal

Question 9

Describe Autocrine Signaling

Answer 9

these signals act on the same cells that released the signal (self signaling)

ex. growth factors in cancer

Question 10

Describe Synaptic Signaling

Answer 10

acts locally to affect nearby cells

basically paracrine signaling BUT with neurotransmitters

ex. Ach in synapses

Question 11

Describe direct cell Signaling

Answer 11

2 cells physically contacting one another to conduct signaling

Ex. (in immune cells) Ag-presenting cells to T cells

Question 12

Name the 4 overall cellular responses to signals

Answer 12

survive

Grow/divide

Differentiate

die via apoptosis (this can either be signaled or occurs after there are no signals sent to this cells for a predetermined amount of time)

Question 13

proteins, small peptides, AA derivatives, hydrophobic molcules (steroid hormones like estrogen), and even gases (like NO) are all examples of what?

Answer 13

Ligand signalling molecules

Question 14

What are the 2 main categories of signaling molecule ligands?

Answer 14

small lipophilic molecules (steroid hormones)

Water soluble molecules (hydrophilic ; growth factors)

Question 15

Why is NO useful for preventing heart attacks?

Answer 15

it signals for Guanidyl cyclase to produce cGMP

cGMP relaxes the muscles in blood vessels

Question 16

True or false, specific ligands can only induce responses for their specific receptors.

Answer 16

False.

the same ligand can produce several different responses

basically, 1 ligand can trigger several but receptors only activate for their specific ligand

Question 17

Most signaling molecules are ____ which means _____. what types of molecules can diffuse across the cell membrane?

Answer 17

hydrophilic; they require cell surface receptors

small hydrophobic signaling molecules. they bind to intracellular receptors

Question 18

the cytoplasmic domain of a cell surface receptor is responsible for what part of the signaling process?

Answer 18

they initiate the signal via a change in conformation

Question 19

Once an intracellular receptor is activated via the biding of the ligand, how do they affect genes in the nucleus? what must be present in order for this to happen?

Answer 19

the “DNA-binding domain” of the intracellular receptor binds to a specific section of the cell’s DNA and induces the transcription of a target gene

coactivator proteins must be present

Question 20

In order to be activated, intracellular receptor molecules must have the ligand bind to them. What happens when the ligand binds to the intracelluar receptor?

Answer 20

the inhibitory protein that was previously bound to the intracellular receptor, unbinds and dissociates with the intracellular receptor

Question 21

What is the major class of surface receptors that mediates the type of cell signaling that requires transmembrane receptors?

Answer 21

G-protein coupled receptors

Question 22

What is the major class of surface receptors that mediates the type of cell signaling that requires transmembrane receptors? what are the 3 components of these?

Answer 22

G-protein coupled receptors

extracellular domain

Transmembrane domain

Cytoplasmic domain

Question 23

What is a heterotrimeric protein composed of 3 subunits (alpha, beta, and gamma)?

Answer 23

G-proteins

Question 24

What is the downstream enzyme adenylyl cyclase an example of? What does adenyly cyclase generate?

Answer 24

an effector

cAMP

Question 25

What is commonly characterized by it’s 7 transmembrane alpha helices?

Answer 25

G protein-coupled receptors

Question 26

GPCR activity (g protein coupled receptors) form _____ ______ which acts on an effector enzyme to form a 2nd messenger. Once the second messenger reaches it’s targets, it elicits a _____ ____.

Answer 26

Trimeric G protein

Biological response

Question 27

List the steps of G-protein relaying signals

Answer 27

1. ligand binds to receptor
2. conformational change occurs in the receptor
3. receptor binds to G protein
4. receptor then acts as a GEF
5. the G alpha protein’s GDP is “kicked out” and replaces by GTP
6. G alpha is now active and binds to the effector molecule in order to activate it

Question 28

What happens after G-protein relaying signals have activated the effector molecule?

Answer 28

the GTP that was bound to G alpha is hydrolyzed into GDP

then G alpha returns to it’s inactive step in order to be recycled for the next signal

Question 29

When the activated receptor protein is acting as GEF, describe how it makes GTP bound instead of the GDP that is initially bound.

Answer 29

the initially bound GDP is “kicked out” and replaced by an entirely new GTP molecule

(This is NOT the GDP being phosphorylated into a GTP)

Question 30

What does Cholera toxin cause sever diarrhea, in terms of it’s molecular interaction with cells.

Answer 30

Cholera toxin modifies G protein by keeping the G alpha in the GTP active form

this makes pathways less active and pumps Cl- and H2O our of cells in the intestine

Question 31

How does cyclic AMP and PKA work to bring about a response?

Answer 31

cAMP activates PKA by phosphorylation

once activated, PKA will phosphorylate proteins to either activate or inactivate them

Question 32

Describe PKA’s subunits when it is active and inactive. relate how cAMP effects this.

Answer 32

Active PKA: 2 catalytic subunits

Inactive PKA: 4 subunits, 2 are catalytic, and the other 2 are regulatory subunits that keep the catalytic subunits inactive

cAMP binds to the 2 regulatory subunits, which allows the 2 catalytic subunits to dissociate and become active

Question 33

Activation/inactivation of enzymatic target proteins, Alteration of intracellular localization of target proteins, and alteration in abundance of target proteins are all examples of what? what triggers these outcomes?

Answer 33

regulation of proteins via the phosphorylation activity of activated PKA

PKA adds 2 negative charges and can change the conformation of a protein it is acting on

Question 34

during a fight or flight response, what does epinephrine do?

Answer 34

it activates PKA, which then has several downstream effects to generate lots of ATP.

Question 35

what does the term “amplification mean when dealing with the cAMP pathway?

Answer 35

it describes how one ligand binding to a receptor can trigger the activation of several adenylyl cyclase proteins which all act on their own effector proteins

Question 36

Describe how GRK’s and arrestin can desensitize a signal

Answer 36

GRK’s phosphorylate the receptor such that arrestin will come bind to the 3rd intracellular loop of the receptor

the binding of arrestin prevents G alpha from interacting with the 3rd loop of the receptor

Since G alpha cannot interact with the receptor, G alpha-GDP will not be able to be converted to g alpha-GTP