Lec 2 Cell Signaling and Cell Membrane

Question 1

why do we need cell receptors and channel?

Answer 1

Everything cannot just cross the cell membrane, therefore need these to conduct signals from the extracellular space inside the cell

Question 2

intracellular events that transform extracellular signals into intracellular signals is called what?

Answer 2

Transduction

Question 3

What Type of Model:
ligand binds cell membrane receptor, activates intracellilar protein assocaited with receptor, goes on to activate a mechanism forming a second messenger
Second messenger activates another protein (can be an effector)

Answer 3

Intracellular Signaling Model

Question 4

What do Effectors do?

Answer 4

They can activate or inactive other biochemical signaling cascades

They can be protein kinases and transcription factors for example

Question 5

Why do we need to terminate signaling?

Answer 5

Can ruin homeostasis if it stays on without regulation

Question 6

How is Termination achieved in the Intracellular Signaling Model?

Answer 6

1. concentration of messenger ligand decreases
2. cell membrane receptor not activated
3. protein associated to cell membrane - inactivated
4. protein/enzyme no longer produces/increases concentration of 2nd messenger
5. 2nd messenger inactivation - no longer activates any effectors downstream

Question 7

What do 2nd messengers do?

Answer 7

Used to amplify the effect of the 1st messenger

Question 8

Types of Cell Membrane Receptrors (3)

Answer 8

• Ion-Channel-Coupled Receptors (need ions to be activated ex. Na, K)
• G-Protein-Coupled Receptors (GPCR)(receptor with G protein associated to it)
• Enzyme-Coupled Receptors (whatever binds to receptor activates an enzyme)

Question 9

Structure of GPCRs

Answer 9

Receptor:
* integral transmembrane protein, spanning 7 times

G Protein:
* 3 subunits: alpha, beta and gamma

Question 10

Unstimulated/Inactive GPCR

Answer 10

alpha bound to GDP
Beta and gamma bound to alpha
(becomes inactived when alpha subunit hydrolyzed GTP to GDP)

Question 11

Stimulated/Activated GPCR

Answer 11

alpha released GDP replacing with GTP
alpha replaced with GTP released beta and gamma

the activated alpha, and betta gamma subunits then go on to effect areas down signaling pathway

Question 12

Gs GPCR

Answer 12

• 1. ligand binds receptor associated with Gs
• 2. Gs alpha released GDP binds GTP and releases beta gamma
• 3. Activated Gs alpha binds adenylyl cyclase - activating it
• 4. Activated adenylyl cyclase converts ATP to cAMP
• 5. cAMP binds PKA inhibitors allowing PKA to work
• 6. PKA phosphorylates effector proteins (CREB)

Question 13

How is cAMP formed?

Answer 13

Enzyme - adenylyl cycles
removed 2Pi making it cyclic

Question 14

How is cAMP turned off?

Answer 14

enzyme - cyclic AMP phosphodiesterase
breaks bond giving cAMP cyclic structure forming 5’-AMP (inactive)

Question 15

Which G-proteins use the alpha subunit activity to impact the 2nd messenger?

Answer 15

Gs, Gi, Gq, Gt (all of them)

Question 16

Which G-proteins use the beta,gamma subunit activity to impact the 2nd messenger?

Answer 16

Gi (exception to alpha unit)

Question 17

Gs enzyme and 2nd messenger:

Answer 17

enzyme = adenylyl cycles
2nd messenger - cAMP

Question 18

Gs biochemical effect/impacts:

Answer 18

cAMP (2nd messenger) activates PKA effector -> phosphorylation

invovled in glycogenolysus, thyroid hormone synthesis… many more

Question 19

Gi (alpha) enzyme and 2nd messenger:

Answer 19

enzyme - adenylyl cycles (INHIBITED)
2nd messenger - cAMP - DECREASED production directly due to inhibited adenylyl cyclase

Question 20

Gi (alpha) biochemical effect/impacts:

Answer 20

Effect: PKA (effector) activation decreases
Impacts: inhibits Gs

Question 21

G1 (beta gamma) enzyme and 2nd messenger:

Answer 21

no enzyme or 2nd messenger!
opens K+ channels

Question 22

Gi (beta gamma) biochemical effects/impacts:

Answer 22

Effect: more negative membrane potential
Impacts: reduced HR (heart rate)

Question 23

Gq (alpha) enzyme and 2nd messenger:

Answer 23

Enzyme = phospholipase C (activated)
2nd messeger = IP3 and DAG (increased production from activated phospholipase C)

Question 24

Gq (alpha) biochemical effect/impact:

Answer 24

Effect:
IP3 causes Ca2+ to release from ER
DAG activates PKC

Question 25

Gt (alpha) enzyme and 2nd messenger:

Answer 25

Enzyme: cGMP phosphodiesterase
2nd messenger: cGMP (decreased by enzyme)

Question 26

Gt (alpha) biochemical effect/impact:

Answer 26

Effect: Na+ channels close, more negative membrane potential
Impacts: detection of light

Question 27

Gq GPCR pathway:

Answer 27

1. ligand binds receptor assocaited with Gq
2. Gq alpha activated (release GDP bind GTP) activated enzyme phospholipase C
3. phospholipase C cleaves membrane bound PIP2 -> IP3 and DAG
4. IP3 activated Ca2+ release from ER (Ca2+ moves to cytosol)
5. Ca2+ and membrane bound DAG activate PKC
6. PKC (2nd messenger activated effector) modulates activity of other effectors

Question 28

In Gi (beta gamma) what does the opening of K+ channels do?

Answer 28

Brings cell membrane potential closer to K Nernst potential = -90mV
The cell is less ‘active’ at this charge
this is called hyperpolarization

Question 29

Enzyme coupled receptor

Answer 29

transmembrane proteins with ligand-binding domain on outer surface of plasma membrane (ex. Tyrosine Kinase)

Question 30

receptor which autophosphorylates itself due to ligand binding causing dimerization

Answer 30

Receptor tyrosin kinase

Question 31

Ligand examples for RTK (receptor tyrosine kinase)

Answer 31

insulin, growth factors, cytokines

Question 32

RTK Signaling Options:

Answer 32

Phospholipase C
* once receptor is phosphorylated this Gq pathway with phospholipase C and directly activate PLC

Ras Cascade:
*Ras encouters activated RTK it binds GTP (activation)
* Ras activates Raf -> goes on to activate MAP kinases
* Ras inactivates itseld by cleaving GTP->GDP