9-11 Cell Signaling II Flashcards Preview

MCBG EXAM 3 FINAL > 9-11 Cell Signaling II > Flashcards

Flashcards in 9-11 Cell Signaling II Deck (32):
1

How does activated phospholipase-CB come about?
2)What does enzyme this make?

1-[Gq]coupled receptor after signaling molecule activates it, it then activates its alpha subunit which stimulates target phospholipase-CB

2)PCB cleaves minor membrane lipid [PI45P2] to make *diacylglycerol* and *inositol 1,4,5triphosphate(IP3)!*

2

Where is the [PI45P2] located?
2)What is the importance of this thing?

1) It's fatty acid tails are embedded in the inner lipid monolayer of the Plasma Membrane

2)[PI45P2] is cleaved by activated phospholipase-CB to make diacylglycerol and IP3

3

PIP Kinase

Kinase that performs the 2nd and last phosphorylation of PI4p to make [PI45P2]
*1st one is done by regular PI Kinase*

4

After [___] is cleaved to finally create diacylglycerol and IP3..what does each of these do?

[PI45P2] is cleaved by phospholipase-CB first to create these two!
A: diacylglycerol=activates Protein Kinase C(also a Ser/Thr required kinase)
B: IP3= INC cytosolic Ca+ by releasing it from ER

5

How does IP3 work in Ca+ release?
2)How does the Plasma membrane assist in this?

IP3 binds to specific ER Ca+ channels which allows for Ca+ to move DOWN its gradient into the cytosol
2)AFTER this occurs PM may also sometimes open its Ca+ channels to allow for Ca+ to rush inside, sustain cytosol levels or replenish ER levels

6

There are ___protein Kinase C forms. 9 of them are activated by ______ but 4 of PKC require ____ and ___

11 protein Kinase C forms
9 require only DAG for activation

4 require DAG AND Ca+ for activation!

7

___ion has to be kept VERY LOW in the cytosol so it can act as a good signaling component when released.

2)What are the 5 ways this ion is kept low in cytosol?

Ca+ is VERY LOW in cytosol so when released from ER it can act as good signaling component and will diffuse DWN its gradient

1. Na+/Ca+exchanger pumps 3 Na+ into cell and 1 Ca+ out
2. Ca+ pump dephosphorylates ATP to pump out Ca+
3. ER membrane Ca+ pump pushes Ca+ inside ER
4. Calcium-binding molecule in cytosol
5. Active import into mitochondria w/H+ symport

8

Describe the Ca+ wave feedback Loop!

2)How is the loop/wave ultimately terminated??

3)What's another name for this feedback loop?

IP3 inducing Small, localized INC in cytosolic Ca+(AKA puffs/sparks) at 1 point can stimulate the opening of OTHER Ca+ Channels nearby!--->waves of Ca+ release mvmnt across the cell!

2)Eventually feedback INHIBITION from lots of Ca+ closes channels and Ca+ is pumped BACK into ER or out of cell

3) [Calcium-induced calcium release]

9

[T or F] Cytosolic Ca+ actually changes and varies over time and space

TRUE!

10

How is the concentration of a signaling molecule related to Ca+ wave oscillations?

2)What is an example of this?

INC in signaling molecule concentration(which stimulates [Gq] protein) will INC transient Ca+ wave oscillation FREQUENCY

2)INC Vasopressin conc. in the liver cell INC FREQUENCY of Ca+ wave oscillations in the cytosol

11

Calmodulin is a super ______protein!
2)Explain how Calmodulin is related to Ca+

3)What does Calmodulin look like?

Calmodulin is a SUPER CONVERSED protein!(Can not change the structure/coding too much).

2)-Calmodulin has 4 Ca+ binding sites BUT ONLY TAKES 2 Ca+ to bind in order to activate
- activated calmodulin complex binds to other enzymes & membrane transport proteins for INC/DEC activity

3)"Boxing Gloves" dimer with an N-terminal and C-terminal end

12

CaM-kinases
2)What's the very special CaM-kinase and why?

*Activated by Calmodulin* these [calmodulin-dependent protein kinases] can carry the Ca+ signal cascade on forward by phosphorylating proteins with serine/threonine AA and altering their activity

"they're [Ca+-Calmodulins] lil helpers"

2)CaM-kinase II is special because it can autophosphorylate ITSELF (on adjacent subunit)! after being partially activated by Ca+-calmodulin binding

13

1)CaM-kinase II is a complex with ___subunits and has the unique ability of ____. How does it do this?

2)What happens when Ca+ DEC around CaM-kinase II?

3) Explain "memory trace"

4)How does this unique feature change the binding affinity of [Ca+-calmodulin]

1)CaM-Kinase II has 12 subunits and can autophosphorylate itself! [Ca+-calmodulin] binds to CaMII which partially activates it kinase and then CAMII phosphorylates its own adjacent subunit! = fully active

2)DEC in Ca+ signal-->calmodulin detaches-->BUT because of the autophosphorylation CAMII enzyme stays active until phosphatase removes tht phosphate :-O

3) a "memory trace" refers to the fact that the Ca+ signal still does it job EVEN W/OUT Ca+ PRESENT

4)Autophosphorylation INC binding affinity for
[Ca+-calmodulin] which delays its release. = even a small subsequent Ca+ signal can quickly reactive the enzyme fully!

14

GREATER FREQ. of Ca+ wave oscillations = _____[INC/DEC] activity of CaM-Kinase II in a cell.
2)Why is this?

3)What happens once CaM-Kinase II reaches this new state caused by GREATER FREQ. in Ca+ wave oscillations?

GRTR FREQ. of Ca+ wave oscillations=INC activity of CaM-Kinase II.

2)CaM-KinaseII interprets freq. of Ca+ oscillations and knows if there is too much time between Ca+ spikes phosphatase cleave its auto-phosphate off/deactivate it. **Less time between spikes allows all of the enzyme to not be completely inactive b4 new spike comes--->more and more of the enzyme will become activated over time

3)Once in it's new "hyper" state cAMKII will only need low freq. of Ca+ signals due to the [Ca+-calmodulin] high affinity binding made from autophosphorylation

15

FYI: The effect a signaling molecule has on a cell doesn't necessarily depend on the signaling molecule itself but the__________

Effect a signaling molecule has on a cell depends partly on which ***set of proteins are available for phosphorylation once the signaling molecule starts the process

16

How does Calmodulin stimulate smooth muscle contraction?

[Ca+-calmodulin] complex together activate Myosin light chain Kinase ------>which produces
Myosin light chain-P------->smooth muscle contraction

17

How does Calmodulin assist in producing Glucose?

[Ca+-calmodulin] complex together activate Phosphorylase Kinase----->which produces
Glycogen phosphorylase-P---->MAKES GLUCOSE!

18

The adrenergic hormones Epinenphrine (_____) and NorEpi (____) are special because they have 9 different ________ and can act on ___ of different tissues with different resulting functions!

Epi(Adrenanline) and NorEpi(Noradrenaline) adrenergic molecules have 9 different G-protein coupled receptors which mean they can act on G-proteins in MULTIPLE tissues with MULTIPLE resulting functions

19

Name the G-protein coupled receptor subtypes AND the main G-protein that's activated for the:

Type [a1] adrenergic receptor family

a1A = Gq activation
a1B = Gq activation
a1D = Gq activation

20

Name the G-protein coupled receptor subtypes AND the main G-protein that's activated for the:

Type [a2] adrenergic receptor family

a2A= Gi/Go activation
a2B=Gi/Go activation
a2C= Gi/Go activation

(**Gi -->STOPS adenyly cyclase)

21

Name the G-protein coupled receptor subtypes AND the main G-protein that's activated for the:

Type [Beta] adrenergic receptor family

B1 = Gs activation
B2 = Gs activation
B3 = Gs/Gi/Go activation "it's special"

22

Agonist

Drugs that ACTIVATE a specific adrenergic receptor

23

ANTagonist

BLOCKS epinephrines ability to bind to an adrenergic receptor by binding more competitively!-->Inactivates Receptor

24

Why is it some drugs can target the [a2A] adrenergic receptor w/out actually binding to its sister receptor [a2B]?

Different adrenergic receptor subtypes[a2A vs. a2C] have hormone bindings sites that are structurally different from one another -->allows hormones to target subtypes

25

Epinephrine hormone has the ability to bind to _____ adrenergic receptors

Epinephrine BINDS TO ALL 9 ADRENERGIC GCPR receptors!

26

Nitric Oxide (NO) is a ____ ____ produced by ______ from _____, ____ and ___ parts.

Nitric Oxide (NO) is a signaling molecule that is produced by Nitric Oxide synthase [NOS]--> using AA arginine, oxygen and NADPH parts.

27

eNOS or NOS3 (Nitric Oxide synthase/NOS) are responsible for making ____. How are these enzymes activated in the 1st place??

[eNOS or NOS3 ] make Nitric Oxide (NO)!
2)They're activated when hormones(like bradykinin or ACTH) activate Gq protein
--->which then stimulates [Ca+-calmodulin] to eventually turn on these NOS enzymes

28

After being produced by _____ in the ______....how does Nitric Oxide (NO) actually does its job of relaxing smooth muscles?

Nitric Oxide synthase(NOS)[eNOS/NOS3] produce NO IN THE ENDOTHELIUM.

1)NO passes thru membranes from endothelium(where it's made) into the Smooth MUScle to activate/bind to heme group of [soluble guanylyl cyclase/SGC]---->

2)this will convert< GTP into cGMP > ------.-->
3)cGMP then activates Protein Kinase G(PKG)------------------>

which phosphorylates select Ser/Thr Proteins in the smooth muscle cells = relaxation/dilation

29

During the synthesis of Nitric Oxide (NO) from ______, ______ and _____. What is the name of the final byproduct which isn't used?

2)Where does NO synthesis/creating naturally occur?

During synthesis of Nitric Oxide (NO) from AA arginine, oxygen and NADPH the byproduct [L-Citrulline] is left over and not used!

2)NO is first made in the ENDOTHELIUM and then it passes into the smooth muscle

30

What are 2 natural molecules which can start up the NO synthesis process?

THESE can start up the NO synthesis process!
1. Bradykinin Hormone
2. Acetylcholine from nerves in vessel wall

31

Draw Out/Visualize the ENTIRE PROCESS of Vascular Relaxation Mediated with Nitric Oxide. [7] :-O

2)This process is _____-dependent

1:Bradykinin or ACTH stimulate coupled receptor to activate Gq-protien
2: Gq-protein activates Phospholipase C which makes DAG and IP3
3: IP3 goes off to cause ER Ca+ release which Ca+ then joins with Calmodulin-->[Ca+-Calmodulin] complex
4:[Ca+-Calmodulin] binds & turns on NOS enzymes which make NO from Arg, O2 and NADPH.
5: NO travels out of endothelium, passes membranes and into smooth muscle cells to activate/binds to heme of SGC

6: SGC converts and cGMP activates PKG
7: PKG phosphorylates select Ser/Thr proteins in smooth muscle cell--->VASODILATION/RELAXATION!

(This process IS ENDOTHELIUM dependent)

32

Describe the ____-INDEPENDENT process of Nitric Oxide Vasodilation/Relaxation in smooth muscle cell

DRUGS like bypass (NO)-endothelium synthesis and PUSHES (NO) DIRECTLY into smooth muscle cell for vasodilation/relaxation process
=
endothelium-INDEPENDENT VASODILATION