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Biochem block 3 > Lecture 2- Cell signaling > Flashcards

Lecture 2- Cell signaling Flashcards

1
Q

What are examples of cell surface receptors

A

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

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2
Q

Are cell surface receptors hydrophobic or phillic

A
  • hydrophillic
  • cannot pass through cell membrane
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3
Q

Cell surface receptors are ___ ____ proteins

A

Integral membrane

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4
Q

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

A
  • activates secondary messengers within the cell
  • leads to signal transduction
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5
Q

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

A

endocytosis to negatively regulate the hormone action

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6
Q
A
  • 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
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7
Q

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

A

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

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8
Q

What are the major classes of transmembrane receptors

A
  1. liganded gated ion channels
  2. enzyme-linked receptors
  3. cytokine receptors
  4. GPCR
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9
Q

example ligand gated ion channels and where we find them

A
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10
Q

Explain enzyme linked receptors

A

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

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11
Q

Two things can happen with enzyme linked receptors

A

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

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12
Q

explain the activation via growth factor binding–> protein phosphorylation

A
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13
Q

explain insulin signaling

A
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14
Q

explain transducer: Ras GTPase and canonical growth factor receptor

A
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15
Q

Explain the Ras activated pathway MAP kinase cascade

A
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16
Q

What are the two enzyme linked signal transduction

A

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

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

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17
Q

Explain cytokine receptors

A
  • 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)
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18
Q

Explain the JAK STAT pathway

A
  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
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19
Q

What binds to the receptors in the JAK STAT pathway

A

cytokines

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20
Q

What are G protein coupled receptors (GPCRs)

A

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

21
Q

what are the ligands that activate GPCR

A

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

Proteins
* TSH
* LH
* FSH
* interleukins
* chemokines

22
Q

What is the response when the ligand is bound

A

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

23
Q

Review: insulin goes through what?

A

Sequential phosphorylation

24
Q

What binds in JAK and STAT

A

cytokines

25
Q

When is RAS activated

A

GTP bounded

26
Q

GPCR takes multiple number of ligands which then…

A

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

27
Q

When is G protein activated and inactivated

A

activated:GTP
inactivated: GDP

28
Q

What happens when GTP binds to teh G protein

A

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

29
Q

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

A

alpha

30
Q

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

A

beta and gamma

31
Q

alpha subunit can activate what two enzymes

A
  • adenylyl cyclase
  • phospholipase C
32
Q

When the adenylyl cyclase is activated what is the response

A

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

33
Q

What happens when phospholipase C is activated?

A

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
34
Q

what do pharmaceuticals majorial target

A

GPCRs

35
Q

How does GPCR regulate so many differenct activites?

A

alpha subunit

36
Q

What is the subclasses of the alpha subunits and their functions

A

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

37
Q

What does ai do

A

ion channels
inhibition cAMP

38
Q

What does as do

A

increase cAMP

39
Q

how do we pick ai or as

A

by the type of ligand that binds

40
Q

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

A

activate as which in return stimulates g protein

41
Q

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

A

activates ai in return to inhibit g protein

42
Q

what are the commone second messengers

A
  • Ca+2
  • 3,5 cyclic AMP and GMP
  • 1,2-Diacylglycerol (DAG)
  • Inositol 1,4,5-triphosphate (IP3)
43
Q

Example how camp regulated protein kinase A

A
44
Q

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

A

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

45
Q

How do we target signaling pathways for drugs

A

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

46
Q

drugs targets G protein coupled receptors (GPCRs)

A
  • inhibit signaling pathways
  • target cell bc of these receptors
  • act as competive inhibitors
47
Q

signal transduction pathway cross-talk

A
  • have gene expression change
  • different amount of protein that is present
48
Q

explain signaling cascade

A

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

49
Q

What are the modes of down regulation of signaling

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

Biochem block 3 (6 decks)

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