Lecture 2- Cell signaling

Question 1

What are examples of cell surface receptors

Answer 1

Growth factors, EGF, Insulin
* Bind outside of cell then brings change inside the cell

Question 2

Are cell surface receptors hydrophobic or phillic

Answer 2

• hydrophillic
• cannot pass through cell membrane

Question 3

Cell surface receptors are ___ ____ proteins

Answer 3

Integral membrane

Question 4

When cell surface receptor have a hormone bound, what happens? and what can it lead to?

Answer 4

• activates secondary messengers within the cell
• leads to signal transduction

Question 5

Cell surface receptors can be internalized by _____ to…..

Answer 5

endocytosis to negatively regulate the hormone action

Question 6

Answer 6

• Growth factors, EGF, insulin binds to the cell surfact receptor
• Signal transuction cascade/pathway occurs to cause phosphorylation cascades or conformational change
• Second messengers turn on transcription of a gene

Question 7

Cell surface receptors have how many domains and what are they?

Answer 7

3 domins
* Extracellular
* transmembrane: through membrane
* intracellua: enzyme activity

Question 8

What are the major classes of transmembrane receptors

Answer 8

1. liganded gated ion channels
2. enzyme-linked receptors
3. cytokine receptors
4. GPCR

Question 9

example ligand gated ion channels and where we find them

Answer 9

Question 10

Explain enzyme linked receptors

Answer 10

signal transduction cascade
* Hormone or Growth factor binds to the extracellular domain of its specific receptor
* Enzyme linked receptorsL receptor binding leads to activation of tyrosine kinase or serine/threonine kinase activity in the cytoplasmic domain of the receptor

Question 11

Two things can happen with enzyme linked receptors

Answer 11

a)leads to sequential phosphorylation of intracellular signaling molecules and transduction of the signal to a biological response
b) activation of GTP binding RAS protein

Question 12

explain the activation via growth factor binding–> protein phosphorylation

Answer 12

Question 13

explain insulin signaling

Answer 13

Question 14

explain transducer: Ras GTPase and canonical growth factor receptor

Answer 14

Question 15

Explain the Ras activated pathway MAP kinase cascade

Answer 15

Question 16

What are the two enzyme linked signal transduction

Answer 16

protein phosphorylation
* example was insulin signaling pathway
* ATP and kinase activity

Ras is an on-odd switch regulated by GTP
* GTP
* NO KINASE

Question 17

Explain cytokine receptors

Answer 17

• Some receptors do not have intricsic kinase activity
• These cytokine receptors are associated with a protein kinase family, JAKS which when autophosphorylated recruit STATs (singal transducers and activators of transcription)

Question 18

Explain the JAK STAT pathway

Answer 18

1. Cytokine binds
2. turn on JAK activity and is auto phosphorylated
3. once JAk is phos, then recruit stat which gets phos (activated)
4. Activated STATs dimerize and translocate to nucleus
5. Bind to promotor region to recruit co-activators to transcribe genes for growth, proliferation, cell fate determination, stem cell renewal

Question 19

What binds to the receptors in the JAK STAT pathway

Answer 19

cytokines

Question 20

What are G protein coupled receptors (GPCRs)

Answer 20

7 transmembrane receptor that is couple with a g protein which has its own subunits (a, b, gamma)

Question 21

what are the ligands that activate GPCR

Answer 21

Ca++
Odorants
pheremones
small molecules
* aa, amines
* n.t., n.s.
* prostaglandins, PAF
* peptides

Proteins
* TSH
* LH
* FSH
* interleukins
* chemokines

Question 22

What is the response when the ligand is bound

Answer 22

Activates g-protein which in returns actives effector membrane enzymes or channels–> activate 2nd messengars

Question 23

Review: insulin goes through what?

Answer 23

Sequential phosphorylation

Question 24

What binds in JAK and STAT

Answer 24

cytokines

Question 25

When is RAS activated

Answer 25

GTP bounded

Question 26

GPCR takes multiple number of ligands which then...

Answer 26

activates G protins that has 3 domains which then activates the membrane effector to create 2nd messengers

Question 27

When is G protein activated and inactivated

Answer 27

activated:GTP inactivated: GDP

Question 28

What happens when GTP binds to teh G protein

Answer 28

GTP binds to the alpha subunit and beta+gamma dissociate away from alpha

Question 29

Which G protein subunit(s) is associated with enzyme activity?

Answer 29

alpha

Question 30

What subunit(s) works with the opening and closing of ion channels

Answer 30

beta and gamma

Question 31

alpha subunit can activate what two enzymes

Answer 31

* adenylyl cyclase * phospholipase C

Question 32

When the adenylyl cyclase is activated what is the response

Answer 32

ATP activate cAMP (2nd messanger) which then activates the activates protein kinase A to phosphorylation of other targets

Question 33

What happens when phospholipase C is activated?

Answer 33

Cleaves phospholipids to get DAG (2nd messenger ass. with membrane). * DAG can then activate protein kinase C to get protein phosphorylation OR * DAG activates IP3 (inositol triphosphate, 2nd mess) to regulate Ca+2 channels

Question 34

what do pharmaceuticals majorial target

Answer 34

GPCRs

Question 35

How does GPCR regulate so many differenct activites?

Answer 35

alpha subunit

Question 36

What is the subclasses of the alpha subunits and their functions

Answer 36

ai: ion channels, inhibition cAMP as: increase (stimulate) cAMPA aq: phospholipase C ai2: Pho GEFs

Question 37

What does ai do

Answer 37

ion channels inhibition cAMP

Question 38

What does as do

Answer 38

increase cAMP

Question 39

how do we pick ai or as

Answer 39

by the type of ligand that binds

Question 40

hormone or n.t activates adenylyl cyclase to do what?

Answer 40

activate as which in return stimulates g protein

Question 41

hormone or n.t inhibits adenylyl cyclase to does what?

Answer 41

activates ai in return to inhibit g protein

Question 42

what are the commone second messengers

Answer 42

* Ca+2 * 3,5 cyclic AMP and GMP * 1,2-Diacylglycerol (DAG) * Inositol 1,4,5-triphosphate (IP3)

Question 43

Example how camp regulated protein kinase A

Answer 43

Question 44

Patel talked about how back in the day (1993) about decreased and increase signal transduction

Answer 44

decreased signal transduction * decrease gene expression or impaired expression Increased signal transduction * increase gene expression or impaired expression Decrease or increase is not a good thing--> disease cancer is impaired signal transduction

Question 45

How do we target signaling pathways for drugs

Answer 45

Block the receptor * Shut down growth factor * ex. herceptein * blocks receptors so growth decreases Target cancel cell with antibody-tozin conjugate * if you want to target a particular cell type and not affect other ones you use radioisotype * radioisotype is bound to antibody which is bound to antigen which targets receptor

Question 46

drugs targets G protein coupled receptors (GPCRs)

Answer 46

* inhibit signaling pathways * target cell bc of these receptors * act as competive inhibitors

Question 47

signal transduction pathway cross-talk

Answer 47

* have gene expression change * different amount of protein that is present

Question 48

explain signaling cascade

Answer 48

a hormone binding to its receptor activates the signaling cascade--> amplification of signal * hormones can bind to multiple receptros before being degraded * each receptor can activate several enzymes * these enzymes produce seconf messengers * results in transcription of several genes, and other metabolic effects--> ex. uptake of glucose

Question 49

What are the modes of down regulation of signaling

Answer 49

* upcoupling of the receptor from signaling cascade: receptor inactivation * Receptor internalization: endosome * receptor down-regulation: lysosome