Exam 2

Question 1

Signal transduction pathway

Answer 1

When extracellular signal molecule binds to the receptor protein, it activates one or more intracellular signaling pathways or systems.

System depend on intracellular signaling proteins. Their function is to process the signal inside receiving cell and distribute to intracellular targets (effector proteins).

The effector protein is altered in some way by the signal and implement appropriate change in cell behavior.

Examples of effector proteins: transcription regulators, ion channels, components of metabolic pathway or parts of the cytoskeleton.

Question 2

Contact-dependent signaling

Answer 2

Development of complex structured (eye, immune response)

Question 3

Paracrine signaling

Answer 3

Secretion of local mediators rhat act on cells in the local environment.

Autocrine signaling (respond to its own signal). E.g. used to reinforce developmental decision. (Cancer cells)

Question 4

Synaptic signaling

Answer 4

Limited to neurons

Question 5

Endocrine signaling

Answer 5

Long-distance; distribution of hormones via bloodstream.

Hormones are a signaling molecule secreted by the endocrine cell.

Question 6

Describe the two major classes of signaling molecules and how signal characteristics affect receptor location

Answer 6

Different signal characteristicd drive receptor type

Hydrophilic signals, unable to cross the PM, use Cell-surface receptors.

Small hydrophobic signals (steroid hormones) diffuse across the plasma membrane and can activate intracellular receptors

Question 7

Binding specificity

Answer 7

The ability to distinguish closely related substances

Question 8

Agonist

Answer 8

Drug that binds to a receptor and activates the receptor to produce a biological response

Question 9

Antagonist

Answer 9

Drug that binds to receptor, does not induce a response: prevents a receptor activation

Question 10

Binding affinity

Answer 10

Defines the strength of the interaction beteeen the ligand (signaling molecule) and its receptor

Question 11

Kd

Answer 11

Equilibrium binding constant =Kd

Kd = dissociation constant

It is a measure of the affinity if the receptor for its lifand

Kd = [Rfree][Lfree]/[RL]

Kd is = the ligand concentration at 1/2 max binding

Lower the Kd, higher the affinity

Question 12

Do cells need signals to survive?

Answer 12

Yes

If a cell has no signal it will go through apoptosis

Question 13

What is special about acetylcholine relating to cell signaling?

Answer 13

Acrtylcholine can have different effects on different target cells

If they:
1. Use the same receptor
Or
2. Different receptors in use but they both have the signal binding domain

Remember: An extracellular signal has little information content

Question 14

How are responses to a signal molecule programmed

Answer 14

1. Through the receptors that the target cells carry

2. Through the internal machinery to which the receptors are coupled

Question 15

What are the requirements fir a signal to bind to a cell-surface receptor

Answer 15

Must be a transmembrane protein

Must have both extracellular and intracellular domains

Binding to the extracellular domain must lead to a molecular change inside the cell that can be recognized

Question 16

What are the 3 major classes of cell-surface receptors?

Answer 16

1. Ion-channel coupled receptors
   - gated ion channels
2. G-protein couples receptors.
   - work via trimerix G-proteins
   - associated with vision and smell
3. Enzyme coupled receptors
   - enzyme = kinase

Question 17

What are the 3 main types of molecular switches

Answer 17

1. Ligand binding: allostery, allosteric proteins. (Structural change occurs = functional change)
2. Phosphorylation
   - The protein kinase adds phosphate groups
   - The protein phosphatase removes phosphate groups
3. GTP-binding proteins

Question 18

What are the two main groups of protein kinases?

Answer 18

Serine/threonine kinases

Tyrosine kinases

Question 19

What are the two major types of G proteins?

Answer 19

Large trimeric G-proteins: help relay signals from the G-protein receptors that activate them

Small monomeric G-protein: help relay signals from many classes of cell-surface receptors.

Question 20

What is the function of Guanine nucleotide-dissociation inhibitors (GDIs)

Answer 20

Can hold G-protein inactive by inhibiting the release of a bound GDP

Question 21

Function of GTPase-activating proteins

Answer 21

Regulators of G protein signaling (RGS).

Promote dephosphorylation to GDP

Question 22

Function of Guanine nucleotide-exchange factors (GEFs)

Answer 22

Promote bonding of GTP

Question 23

Function of scaffolding proteins

Answer 23

Bring groups of interacting signaling proteins together.

This decreases the possibility of activating the wrong protein

Question 24

Function of modular interaction domains

Answer 24

They mediate interaction between intracellular signaling proteins

Question 25

Describe the major characteristics of a G-protein coupled receptor

Answer 25

Largest family of cell surface receptors Examples: light, odorants, peptides (neurotransmitters), hormones Structure is single polypeptide that is a multi pass transmembrane protein with 7 transmembrane domains Activation of the receptor creates binding site for trimetic G-protein on intercellular side Interaction of the G-protein with the receptor activates the G protein

Question 26

Describe the major characteristics of Trimeric G-Protein

Answer 26

Composed of 3 polypeptides (subunits)  Function in a similar fashion to mono medic GTP-binding proteins Covalently attached lipids found on both the alpha and y subunits

Question 27

Process of G-protein activation

Answer 27

1. Ligand (signaling molecule) binds receptor activating it which causes conformational change that exposes a binding site for G-protein 2. G-protein binds: Receptor acts as the GEF (GDP is ejected, GTP binds) 3. GTP binding activated the alpha subunit causing it to dissociate from the Beta/gamma subunit. This activated the beta/gamma. 4. Both subunits can activate target proteins 5. GTPase activity of alpha subunit, hydrolyses GRP to GDP, inactivates alpha subunit, which reassociates with beta gamma subunit Key concept: both alpha subunit and beta/gamma subunit can relay a signal

Question 28

I’m GPCR pathways, effector proteins are either….

Answer 28

Enzymes that catalyze the formation of second messengers or ion channels

Question 29

Describe the role of Adenylyl Cyclase

Answer 29

It is an effector protein. An enzyme that catalyzes formation of 2 messengers Produces cAMP Membrane bound enzyme Converts ATP into cAMP which is a ubiquitous intercellular messenger (2nd messenger) cAMP works as a ligand to activate other target proteins In order to function as a messenger cells need to be able to quickly change its concentration therefore rapid synthesis and rapid degradation can occur

Question 30

What mediates the effects of cAMP

Answer 30

Protein Kinase A (PKA) Tetramers: 2 regulatory and 2 catalytic domains Binding of cAMP causes dissociation of the two catalytic domains Unmasks the active sites: activated Binding of cAMP to the regulatory subunits is cooperative. Binding of the first cAMP lowers the Kd for binding of the second! This means that small changes in level of cytosolic cAMP can cause proportionately large changes in the amount of active PKA

Question 31

PKA

Answer 31

is a serine/threonine Kinase Will phosphorylate different proteins in different cell types

Question 32

Characteristics of signal that binds to cell surface receptor

Answer 32

Transmembrane Extra cellular and intracellular domain Causes molecular change that can be recognized inside cell

Question 33

The 3 major classes of cell surface receptors

Answer 33

Ion channel receptor G protein coupled receptor Enzyme coupled receptor

Question 34

GPCR

Answer 34

Single poly peptide Transmembrane multi pass Activation of it creates binding site for trimeric G protein Interaction of the G protein with receptor activated the G protein

Question 35

Trimeric G protein

Answer 35

3 polypeptides (alpha subunit and beta/gamma sub unit) Covalently attached lipids found on both the alpha and gamma subunits

Question 36

Effector proteins of GPCR pathways

Answer 36

Enzymes that catalyze formation of second messengers or ion channels

Question 37

Adenylate Cyclase

Answer 37

Produces cAMP Membrane bound Converts ATP into cAMP

Question 38

cAMP

Answer 38

2nd messenger | Works as ligand to activate other target proteins

Question 39

PKA

Answer 39

binding of cAMP causes dissociation of the two catalytic domains: becomes active Small changes in level of cAMP can cause large changes in amount of active PKA PKA is a regulator of cAMP

Question 40

Phospholipase C

Answer 40

Enzyme that cleaves PI 4,5 biphosphate to produce IP3 and DAG

Question 41

IP3 and DAG

Answer 41

2nd messengers IP3 opens Ca++ channels DAG activates protein kinase C

Question 42

Ca++

Answer 42

Acts as an allosteric effector (ligand)

Question 43

Calmodulin

Answer 43

Enzymes ION pumps Protein kinases

Question 44

Dark adapted cells

Answer 44

Have open channels that are depolarized | Increased levels of cGMP

Question 45

RTKs

Answer 45

Important in responses to signals that promote growth Signal binding (activation) causes the receptors to dimerize. Diners can cross-phosphorylate Phosphorylated tyrosines are docking sites for proteins with SH2 and PTB SH3 domains: protein/protein

Question 46

Adaptor proteins

Answer 46

Composed almost entirely of SH2 and SH3

Question 47

Explain how Ras is activated (RTK)

Answer 47

Active when bound to GTP activation of RAS by RTK The activated receptor is bound by Grb2 (adaptor protein) grb2 is bound by the RAS-gef (sos) SOS activates RAS

Question 48

RAS can activate MAPkinase modules

Answer 48

Mitogens are signals that stimulate cell proliferation Kinase cascades allow signal amplification

Question 49

Akt

Answer 49

Critical for cell proliferation and survival