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):

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)!*


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


PIP Kinase

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


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


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


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!


___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


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]


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



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


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


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


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!


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


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


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


How does Calmodulin assist in producing Glucose?

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


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


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


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)


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"



Drugs that ACTIVATE a specific adrenergic receptor



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


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


Epinephrine hormone has the ability to bind to _____ adrenergic receptors

Epinephrine BINDS TO ALL 9 ADRENERGIC GCPR receptors!


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.


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


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


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


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


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)


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