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Biochemistry 2 > biosignaling > Flashcards

biosignaling Flashcards

1
Q

6 features of signal transduction

A
  1. specificity
  2. amplification
  3. modularity
  4. desensitization/adaptation
  5. integration
  6. localization
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2
Q

4 major types of receptors

A
  1. GPCR (G-protein coupled-receptor)
  2. receptor enzyme (tyrosine kinase)
  3. gated ion channel
  4. nuclear receptor
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3
Q

7 steps of GPCR

A
  1. epinephrine binds to its specific receptor
  2. GDP bound to Gsa and activates in GTP
  3. Gsa separates from Gsb, moves to adenyl cyclase and activates it
  4. catalyzation of cAMP by adenyl cyclase
  5. cAMP activates PKA
  6. phosphorylation of cellular proteins by PKA
  7. cAMP is degraded
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4
Q

what activates the PKA

A

cAMP

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5
Q

5 components of PKA

A
  1. regulatory subunit
  2. catalytic subunit
  3. substrate-binding cleft
  4. AKAP
  5. dimerization domain
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6
Q

what cause the cAMP to the PKA

A

when cAMP binds to the R subunit, it undergo a conformational change that moves the autoinhibitory domain of R out of the catalytic domain of C and the complex will dissociateto yiel 2 free catalytically active C subunits

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7
Q

signal control - termination 1 ,what are the two proteins that transform ATP to cAMP and cAMP to AMP

A
  1. adenyl cyclase

2. cyclic nucleotide phosphodiesterase

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8
Q

two exampls of modulators of GTPase activity (that can speed up or slow down the conversion of GTP to GDP)

A
  1. GAP : GTPase activator protein

2. RGS: regulator of Gprotein signaling

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9
Q

what are Raf, cGMP PDE, AC…

A

downstream effector enzymes

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10
Q

in the desensitization, what do Bark (b-adrenergic receptor kinase)

A

it phosphorylates the Ser residues at the carboxyl terminus of the receptor

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11
Q

what do the Barr (B-arrestin)

A

it binds to the phosphorylated carboxyl-terminal domain of the receptor

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12
Q

how the receptor-arrestin enters in the cell

A

by endocytosis

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13
Q

4 different localization of a signal

A

plasma membrane
nucleous
mitochondria
ion channels

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14
Q

what activates phospholipase C (PLC)

A

Gqs linked to GTP

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15
Q

what PLC catalyzes

A

the production of 2 second messenger:

  • diacyglycerol
  • cleaves PIP2 to IP3
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16
Q

real name of IP3

A

inositol 1,4,5-triphosphate

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17
Q

what do IP3 (which is water soluble)

A

it diffuses from the plasma membrane to the endoplasmic reticulum where it will bind to a specific receptor-gated Ca2+ channel, causing it to open

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18
Q

what do Ca2+ and diacylglycerol

A

activates PKC (protein kinase C)

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19
Q

2 major pathways activated by tyrosine kinase receptors

A
  1. MAPK

2. PIP3

20
Q

composition of the receptor tyrosine kinase

A
  • ligand-binding sites on the extracellular domain
  • a single transmembrane helix
  • a cytoplasmic domain with protein Tyr kinase activity controlled by extracellular ligand
21
Q

why the macanism of activation of INSR, PKA and PKC are similar

A

because in every case, a region of the cytoplasmic domain that usually lock the active site is moves out after being phosphorylated

22
Q

what the activation of the receptor tyrosine kinase allows

A

it allows to B subunits to phosphorylate the three Tyr residues on the other B subunits and the three highly charged P-Tyr force a change in the position of the activation loop, away from the substrate-binding site, which become available to bind and phosphorylates target protein

23
Q

what insulin receptor phosphorylates

A

IRS-1 on its Tyr residues

24
Q

MAPK- what bind to the P-Tyr of IRS-1

A

SH2 domain of Grb2. Then Grb2 binds to Sos and then Ras (will cause the change GDP to GTP). so, the order is:
IRS-1, Grb2, Sos, Ras binds to GTP

25
Q

MAPK- activated Ras binds and activates what

A

Raf-1

26
Q

MAPK- Raf-1 phosphorylates ______________ activating it. ___ phosphorylates _____, activating it

A
  1. MEK on two Ser residues

2. ERK, on a Thr and Tyr residue

27
Q

MAPK- where the ERK moves and what does it phosphorylates

A

moves to the nucleous and phosphorylates nuclear transcription factors such as Elk1 (active them)

28
Q

PIP3- what IRS-1 activates

A

PI3K by binding to its SH2 domain

29
Q

PIP3- What PI3K converts

A

it converts PIP2 to PIP3

30
Q

PIP3 bound to what

A

PKB which is phosphorylated by PDK1

31
Q

what PKB phosphorylates

A

GSK3 on a Ser residue, inactivating it

32
Q

what GSK3 can’t do when it is in its inactivate form

A

it cannot convert glycogen synthase (GS) to its inactive form by phosphorylation so GS remains active

33
Q

what PKB stimulates

A

the movement of glucose transporter GLUT4 from internal vesicle to the plasma membrane, increasing the uptake of glucose

34
Q

cross integration : effect of INSR to adrenergic receptor

A
  1. when INSR is activates, its Tyr kinase phosphorylates B-adrenergic receptor on two Tyr residues near the carboxyl terminus + indirectly through activation of PKB that causes the phosphorylation of two Ser residues
    * * effect: lowering the cell’s sensitivity to epinephrine
  2. P-Tyr residues of the adrenergic receptor serve as nucleation point for SH2 domain-containing such as Grb2. Activation of the MAPK ERK is very greater in presence of B-adrenergic receptor
35
Q

what is protein phosphorylation

A

it is the process in which a phosphoryl group (phosphate), donated by ATP, is transfered to an acceptor protein
** catalyzed by a protein kinase

36
Q

what makes ion channels open

A

ligands or change in membrane potential

37
Q

what do Na+K+ATPase

A

maintain the membrane in polarized state (-70 to -50 mV)

38
Q

the direction of the ion depends on what

A

its electrochemical gradient

  • the concentration of the ion on two sides of the cell
  • difference in electrical potential
39
Q

how voltage-gated Na+ channel and what it will cause

A

open when there is a stimulus that depolarized the membrane
- in response to the depolarization of Na+ inside the cell, voltage-gated K+ will open a short time after to repolarize the cell

40
Q

what makes the voltage-gated Ca2+ channel and what it will cause

A

the wave of depolarization

it will triggers the release of acetylcholine by exocytosis into the synaptic cleft

41
Q

what are the receptors (acetylcholine) for cations and anions

A

cations: serotonin and glutamate receptors
anions: glycine receptors

42
Q

4 ligands for nuclear receptors

A

vit D, retinoic acid, steroids,thyroid hormones

43
Q

when they are bind to their ligands and that they did their dimerization, nuclear receptors inside the nucleous will bind to what

A

to a specific regulatory regions called hormones-receptor elements (HREs) in the DNA adjacent to specific genes

44
Q

nuclear receptors attract what

A

coactivator or corepressor protein and with them, regulates transcription of the adjacent genes, increasin or decreasing the rate of mRNA formation

45
Q

6 types of signals cells receive from the environment beyond the plasma membrane

A 
hormones
neurotransmetteurs
pheromone
touch
light
antigens
46
Q

definition of receptor

A

a membrane-bound or soluble protein or protein complex, which exerts a physiological effect (intrinsic effect) after binding its natural ligand

Biochemistry 2 (17 decks)

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