Cell Signaling

Front 1

Why do cells need to respond to signals?

Back 1

Need to respond to a changing environment: Adaptation or a cellular response is critical for survival.
Cells need to communicate with each other.
To Modify cellular metabolism, function, movement
To modify gene expression, development

Front 2

How does glucose act as a signal to yeast cells

Back 2

Glucose acts as a signal to yeast cells to increase number of glucose transporters and enzymes allowing efficient uptake and use of glucose

Front 3

What is Auxin

Back 3

a signaling molecule transmitted from cell to cell and inhibited by the light
(darwin and son investigated phototropism, cell-to-cell communication mediated by Auxin)

Front 4

What are the features of signal transducing systems?

Back 4

Specificity
Amplification
Desensitization/Adaptation
Integration

Front 5

define Specificity within a signal transducing system

Back 5

Signal molecule fits binding site on its complementary receptor, other signals do not fit.

Front 6

Define Amplification in terms of signal transducing systems

Back 6

When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade.

Front 7

Define Desensitization/Adaption in terms of signal transducing systems

Back 7

Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface.

Front 8

Define Integration in terms of signal transducing systems

Back 8

When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger X, or the membrane potential Vm the regulatory outcome results from the integrated input from both of the receptors.

Front 9

What are the five types of signals relayed between cells

Back 9

Direct intercellular signaling
Contact-dependent signaling
Autocrine signaling
Paracrine signaling
Endocrine signaling

Front 10

Define Direct intercellular signaling

Back 10

Cell junctions allow signaling molecules to pass from one cell to another

Front 11

Define Contact-dependent signaling

Back 11

Some molecules are bound to the surface of cells and serve as signals to cell coming in contact with them.

Front 12

Define Autocrine signaling

Back 12

Cells secrete signaling molecules that bind to their own cell surface or neighboring cells of the same type.

Front 13

Define Paracrine signaling

Back 13

Signal does not affect cell secreting the signal but does influence cells in close proximity (synaptic signaling)

Front 14

Define Endocrine signaling

Back 14

Signals (hormones) travel long distances and are usually longer lasting

Front 15

What are three stages of cell signaling

Back 15

1. Receptor activation when signaling molecule binds to receptor.
2. Signal transduction when the activated receptor stimulates sequence of changes -- signal transduction pathway
3. Cellular response including the alteration of activity of one or more enzymes, the altered structural protein function, the change of gene expression.

Front 16

What is the cellular response to the alteration of activity of 1 or more enzymes

Back 16

Altered metabolism or other cell functions

Front 17

What is the cellular response to the alteration of structural protein function

Back 17

Altered cell shape or movement

Front 18

What is the cellular responce to a change in gene expression

Back 18

Altered gene expression changes the amounts of proteins in the cell

Front 19

What is a Ligand?

Back 19

a signaling molecule that rapidly binds noncovalently to a receptor with a high degree of specificity.

Front 20

What effects do ligands have on receptors and what is a hormon receptor complex?

Back 20

Ligands alter receptor structure - a conformational change.
Hormone-receptor complexes are activated receptors that can initiate cellular responses

Front 21

What are enzyme linked receptors

Back 21

cell surface receptors found in all living species, the Extracellular domain binds signal (hormon/ligand) causes intracellular domain to become a functional catalyst.
an example are protein kinases

Front 22

what is Kd

Back 22

Kd is a measure of the affinity of a ligand for its receptor (molecular complementarity -- specificity). The concentration of ligand at half its receptors occupied, Kd, is experimentally determined.

Front 23

What are agonists

Back 23

Agonists are structural analogs that bind to a receptor and mimic the effects of its natural ligand.

Front 24

what are antagonists

Back 24

Antagonists are analogs that bind the receptor without triggering the normal effect and thereby block the effects of agonists.

Front 25

is it necessary for most receptors to be occupied by a ligand to have a max physiological response?

Back 25

no, the max physiological response occurs when only a fraction of receptors are occupied by a ligand. Well before Kd for ligand binding is reached.

Front 26

What determines the sensitivity of a cell to external signals?

Back 26

the number of surface receptors and their affinity for ligand.

Front 27

What is transduction?

Back 27

Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

Front 28

What are the benifit of signal transduction involving multiple teps?

Back 28

multistep pathways can amplify a signal: a few moleculs can produce a large cellular response
multistep pathways provide more opportunities for coordination and regulation of the cellular response.

Front 29

in signal transduction pathways, what molecules generally relay a signal from receptor to response?

Back 29

mostly proteins

the receptor activates another protein, which activates another and so on until the protein producing the response is activated (cascade)

at each step, the signal is transduced into a different form, usually a shape change in a protein

Front 30

what are six types of signal transducers?

Back 30

G protein-coupled receptor
Receptor tyrosine kinase
Receptor guanylyl cyclase
Adhesion receptor (integrin)
Gated Ion Channel
Nuclear receptor

Front 31

What si a G protein-coupled receptor

Back 31

External ligand binding to receptor, activates an intracellular GTP-binding protein which regulates an enzyme that generates an intracellular second messenger.

Front 32

What is receptor tyrosine kinase?

Back 32

Ligand binding activates tyrosine kinase activity by autophosphorylation

Front 33

What is Receptor guanylyl cyclase

Back 33

ligand binding to extracellular domain stimulates formation of second messenger cyclic GMP

Front 34

What is Adhesion receptor (integrin)

Back 34

Binds molecules in extracellular matrix, changes conformation, thus altering its interaction with cytoskeleton

Front 35

What is a gated ion channel

Back 35

opens or closes in response to concentration of signal ligand or membrane potential.

Front 36

What is a nuclear receptor

Back 36

Steroid binding allows the receptor to regulate the expression of specific genes.

Front 37

some facts about G-protein coupled receptors (GPCR)

Back 37

common in eukaryotes
protein contains 7 transmembrane segments
Activated receptor binds to G protein
Releases GDP and binds GTP instead
GTP causes G protein to disassociate
Subunit and b/g dimer interact with other proteins in a signaling pathway

Front 38

What is the role of Guanine exchange factor?

Back 38

They function as activators of small GTPases. GEFs activate G proteins by promoting this nucleotide exchange

Front 39

In many pathways, the signal is transmitted by a cascade of ____________.

Back 39

protein phosphorylations

Front 40

what do protein kinases do?

Back 40

protein dinases transfer phosphates from ATP to protein, a process called phosphorylation

Front 41

What do protein phosphatases do?

Back 41

protein phosphatases remove the phosphates from proteins, dephosphorylation

Front 42

what acts as a molecular switch, turning activities on and off?

Back 42

phosphorylation and dephosphorylation systems

Front 43

What is a pathways first messenger?

Back 43

the extracellular signal molecule that binds to the receptor is a pathways first messenger

Front 44

What is a signal pathway's second messenger?

Back 44

second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion

Front 45

what pathways do second messengers participate in?

Back 45

second messengers participate in pathways initiated by G protein coupled receptors and receptor tyrosine kinases
cAMP
Ca2+
Diacylglycerol and inositol triphosphate

Front 46

what are
cAMP
Ca2+
Diacylglycerol and inositol triphospate
examples of?

Back 46

second messengers

Front 47

what does cAMP stand for

Back 47

Cyclic adenosine monophosphate

Front 48

what is the signal transduction via cAMP?

Back 48

its the signal binding to GPCR activating G protein to bind GTP causing dissociation.
One type of subunit binds to adenylyl cyclase stimulating synthesis of cAMP
One effect of cAMP is to activate protein kinase A (PKA)
Activated catalytic PKA subunits phosphorylates specific cellular proteins
When signaling molecules are no longer produced, eventually effects of PKA are reversed

Front 49

what are the two advantages of cAMP

Back 49

signal amplification -- binding of signal to single receptor can cause the sythesis of many cAMP that activate PKA, each PKA can phosphyrlate many proteins

Speed -- in one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal

Front 50

All about signal transduction via Ca2+

Back 50

Cells maintain a large Ca2+ gradient
2 types of calcium pumps
When calcium channels open, an influx of Ca2+ acts as a second messenger

Front 51

What are some examples of signal transduction via Ca2+ in plants and animals?

Back 51

Plants: phototropism, opening and closing of stomata, gravitropism

Animals- nerve transmission, muscle contraction, secretion of digestive enzymes

Front 52

where are high concentrations of Ca2+ found in the cell?

Back 52

the Extracellular fluid, ER Lumen, and mitochondrial Matrix.

Front 53

All about Signal transduction via diacylglycerol and inositol triphosphate

Back 53

Second way for an activated G protein to influence signal transduction pathways

A subunit can activate phospholipase C
Diacylglycerol (DAG) and inositol triphosphate(IP) are made from plasma membrane phospholipid
Ca2+ channels in ER open
Variety of effect of Ca2+ on cell behavior

see diagram...

Front 54

what is the general structure of G protein coupled receptors?

Back 54

All G protein–coupled receptors (GPCRs) contain seven membrane-spanning regions with their N-terminal segment (NH3+) on the exoplasmic face and their C-terminal segment (COO-) on the cytosolic face of the plasma membrane
All receptors of this type contain seven transmembrane α-helical regions. The loop between α helices 5 and 6, and in some cases the loop between helices 3 and 4, which face the cytosol, are important for interactions with the coupled G protein.

Front 55

What hormone signals the need to fight or flee?

Back 55

Epinephrine

Epinephrine, which binds to two types of GPCRs, is particularly important in mediating the body’s response to stress, such as fright or heavy exercise, when all tissues have an increased need for glucose and fatty acids. These principal metabolic fuels can be supplied to the blood in seconds by the rapid breakdown of glycogen in the liver (glycogen-olysis) and of triacylglycerol in the adipose storage cells (lipolysis).

Front 56

When does Epinephirne action begin?

Back 56

When the hormone binds to Adrenergic receptors which of are of four general types α1, α2, β1, and β2, defined by differences in their affinities and responses to a group of agonists and antagonists

Front 57

Where are β-adrenergic receptors found and what responses to epinephrine does it mediate

Back 57

β-adrenergic receptors on muscle, liver, andadipose tissue. These receptors mediatechanges in fuel metabolism, including theincreased breakdown of glycogen and fat.

Front 58

Where are α-adrenergic receptors found and what responses to epinephrine does it mediate

Back 58

α-adrenergic receptors on smooth muscle cells in kidneys, GI etc. Binding to thesereceptors causes arteries to constrict

Front 59

how is the long C3 loop critical to interaction with G protein?

Back 59

The C3 loop determins the specificity of G protein binding when compaired to alpha 2 Adrenergic receptor and beta 2

Front 60

for the effector Adenylyl cyclase, what is the second messenger, Gα class, and the Receptor example?

Back 60

cAMP (increased), Gαs, and β-adrenergic (epinephrine) receptors: receptors for glucagon, serotonin, vasopressin

Front 61

for the effector Adenylyl cyclase K+ channel (Gbetay activates effector), what is the second messenger, Gα class, and the Receptor example?

Back 61

cAMP (decreased) Change in membrane potential, Gαi, α2-Adrenergic receptor Muscarinic acetylcholine receptor

Front 62

for the Gα class Gαolf, what is the associated effector, what is the second messenger, and the Receptor example?

Back 62

Adenylyl cyclase, cAMP (increased) Oderant receptors in nose.

Front 63

for the Gα class Gαq, what is the associated effector, what is the second messenger, and the Receptor example?

Back 63

Phospholipase C, IP3'DAG(increased), α1-Adrenergic receptor

Front 64

for the Gα class Gαo, what is the associated effector, what is the second messenger, and the Receptor example?

Back 64

Phospholipase C, IP3'DAG (increased), Acetylcholine receptor in endothelial cells

Front 65

for the Gα class Gαt, what is the associated effector, what is the second messenger, and the Receptor example?

Back 65

cGMP phosphodiesterase, cGMP (decreased), Rhodopsin (light receptor) in rod cells

Front 66

Ligand-Gated Ion channels: three random facts

Back 66

found in plant and animal cells
Ligand binding causes ion channels to open and ions to flow through the membrane
Animals- signals between nerve and muscle cells, between 2 nerve cells, Ca2+ uptake

Front 67

what kind of receptors in the heart muscle activate G proteins that open K channels

Back 67

Muscarinic Acetylcholine receptors in the heart muscle activate G proteins that open K channels. Hyperpolarization reduces frequency of cardiac muscle contraction

Front 68

Epinephrine, Glucagon, ACTH are examples of ___________ that ________________

Back 68

stimulatory hormones that activate Adenylyl Cylase

Front 69

PGE1 and Adenosine are examples of ___________ that _______________

Back 69

Inhibitory hormones that inhibit Adenylyl Cylase

Front 70

how does cAMP activate PKA?

Back 70

by releasing Cat subunits. Regulatory subunits have pseudosubstrate seq which keeps cat subunits inactive

Front 71

Intracellular receptor proteins are found in the cytosol or nucleus of target cells, what kind of chemical messengers can activate receptors?

Back 71

small or hydrophobic chimical messengers can readily cross the membrane and activate receptors

Front 72

what are two examples of hydrophobic messengers?

Back 72

steroid and thyroid hormones of animals

Front 73

An activated hormone-receptor complex can act as a _______________, turning on specific genes

Back 73

transcription factor

Front 74

How does Estrogen act with an intracellular receptor?

Back 74

estrogen passes through membrane and binds to receptor in nucleus
Dimer of estrogen-receptor complexes binds to DNA to activate transcription of specific genes.

Front 75

How does Auxin act as an intracellular receptor

Back 75

Binding of auxin in the cytosol activates TIR1
Gene regulation is not direct, but causes breakdown of inhibitory proteins,
with gene inhibition relieved, genes are transcribed.

Front 76

What three classes of organisms have a two component regulatory system -- cellular response?

Back 76

Bacteria, fungi, and plants. (not animals)

Front 77

What are the two components of the two component regulatory system found in bacteria fungi and plants

Back 77

Sensor Kinase, an Enzyme linked receptor that hydrolyzes ATP and phosphorylates- phosphate group transferred to response regulator

Response Regulator: regulates expression of many genes

Front 78

What is NarQ/NarL?

Back 78

A two component regulatory system
Senses presence of nitrate (NO3- and nitrite (NO2-)
Binding phosphorylates NarQ
 Transfers phosphate to NarL (response regulator)
 Activates genes involved in nitrate/nitrite metabolism and
transport

Front 79

Insulin and the Insulin receptor result in a

Back 79

hormon induced dimerization leading to a Cross phosphorylation, and an Activated JAK2 (receptor) Which follows an enzymatic reaction and amplification. The phophorylated IRS proteins follow protein protein interaction resulting in localized phosphoinositide 3 kinase. This enzymateic reaction is amplified resulting in phosphotidylinositol-3-4-5-triphospate (PIP3) which goes through a protein-lipid interaction leading to an Activated PIP3-dependent protein kinase - another enzymatic reaction and amplification results in an Activated AKt protein kinase eventually increasing the glucose transporter on cell surface

Front 80

Signal integration, four possibilities

Back 80

Pathway leads to a single responce
Pathway branches leading to two responses
Cross-talk occurs between two pathways, resulting in one response
Different receptor (same signaling molecule) leads to a different response.