Cell Sigs

Question 1

Cam Kinase II

Answer 1

Calcim calmodulin binds regulatory part of CamKII, conformational change = autophosphorylate, remain active.

Question 2

How to inactivate CamKII?

Answer 2

Phosphatase activity

Question 3

Visual cycle

Turn on

Answer 3

Rhodopsin (GPCR) —> Transducin, convert light in disk membranes of rod cells.
Dark = NaK channels open, light  cis to trans retinal.
GTP binds transducin, dissociate from By-dimer.
Activates PDE (which has catalytic site). PDE hydrolzes cGMP to GMP (reducing levels below what is needed to keep channels open. 
CNG channels close (no influx of NaCa) hyperpole.
Continued efflux Ca through NaCa2 exchanger though.

Question 4

Visual cycle

Turn off

Answer 4

RECOVERY due to decreased Ca++ levels.
RK phosphorylates CTD of rhodopsin.
Allows arrestin bind+internalize rhodopsin.
Recoverin’s inhibition of RK i inhibited, aka RK works.
Or GAP inactivating alpha transducin, RGS GTPase.
Or cGMP PDE turned off by low Ca++ levels.
Or GCAP on bc low Ca++, turns on GC to remake cGMP (using GTP).

Question 5

How does cell membrane guanylate cyclase receptor work? Gcap

Answer 5

Ligand binding extracell domain Nlinked glycosylation.
Binds ANP.
Increased cGMP+activated PKC.
Hypovolemia, hypotension.
Inhibits Na+ reabsorption
~~~~
Atp allosteric activates for conform change, affinity for receptor ligand decreases afterwards.
Dephosphoryla1tion makes receptor inactive

Question 6

Recycing of GCAP

Following isomerization and rlease from opsin protein

Answer 6

All trans retinal reduced to all trans retinol.
Travel back to retinal pigment epithelium .
Esterified by lecithin retinol transferae
Stored as retinyl ester.

Question 7

What is TGFB receptor and what is its purpose?

Answer 7

It is a ser/thr kinase receptor
Purpose of the signaling in adult cells is to stop cell cycle progression - halts cells from making the G1/S phase transition.
3 domains, N terminal EC, TM, and cyto S/T kinase.
Ligand is BMP bone morphogenic protein.
Phosphory Type I receptors GS loop activates kinase, and phosphorylates R-SMaD at 2 C terminus SErines, allows it to complex with SMaD 4 (CoSMaD).

Question 8

ISMaD

Answer 8

Ultimately expressed as1 product of smad signals. Competitively binds type I receptors preventing RSMaD binding.
Recruits E3 ubiquin ligases Smurf I and Smurf 2 leading to degradation via protease.
Binds R smad to prevent complex formation with co smad.
In nucleus, I smad inhibits Smad DNa complex formation.
Ser/thr phosphatases can also inhibit smad signaling independent of I smad.

Question 9

MH-I

Answer 9

Mad hmology, dna biding domain, assists in dna binding with beta hairpin sturcture. R and cosmads have this, I smad does not have MH-I

Question 10

MH2

Answer 10

Mad homology
Smad smad interaction, transcriptonal activation. Type I receptors packet.
Surface of R smad the MH2 domain has multiple contiguous hydrophobic patches aka hydrophonic corridor, site for multiple interactions.

Question 11

C-I

Answer 11

Dag binding domain containing pseudosubstrate that PKC binds and is inactive rendered.

Question 12

JaK homogly domains
Socs box promotes degradation via interaction with proteasomes.
always in C termini

Answer 12

MEK = dual specific kinase, phosphoryltes Thr and TYR residues. Most kinases are either ser Thr or ser TYR.

aKT=PKB
1

Question 13

JaKstat

Answer 13

2 cataylatic domains pseudo kinase and kinase domain KI, other was 2
Binds alpha interferon. Jaks cross phosphorylate each others tyr. Activated . Then stats dock on specific phosphotyr, and jaks phosphorylate those too.
Stats dissociate and dimerize via SH2 domains
Stats translocate to nuclues, binds DNa and regultory. End result is target gene transcription.
Can trn off cytokine signaling with tyr phosphatases Jak receptor, stat proteins, or SOCS N terminal binds Jak, Sh2 domain SOcs box.

Question 14

How does socs work

Answer 14

The proteins compete with binding sites of SH2 tyr domains, binds to the catyltic sites of Jak, recruite proteasome for degradation of reeptor and jak.

Jak mutations include myeloproliferative diseases like polycthemia vera, essential thrombocythemia
Excessive rbcs pltelets, granulosites in absense of cytokine simulation, risk of thrombosis abnormal bleed, leukemia.
Or loss of function mutations immunocompromised.

Question 15

1G protein coupled receptors are desensitized

Answer 15

Via phosphorylation by G protein coupled receptor kinases.

Question 16

Pertussis toxin prevents activation of

Answer 16

Galpa(a) and dimer protein

Question 17

Role of PLC

Answer 17

Results in activateion of PKC and calcium calmodulin kinase.

Question 18

Protein kinase C PKC in its inactive form has?

Answer 18

A. Pseudosubstrate domain occypying its substrate binding site.

Question 19

Absoprtion of light by rhodposin leads to

Answer 19

Close of cGMP dependent soium calcium channels.

Question 20

Name the binding partners of 
SH2
PTP
SH3
PH
C2

Answer 20

SH2 Tyr residues phosphorylated
Also phosphorylted tyr’s
SH3 prolines
PH PI
C2 calcium

Question 21

What happens to blood pressure when you have decreased binding of aNP to receptor?

Answer 21

Inability to decrease blood pressure, hypertension, may be due to mutation of kinase hhomogy domains.

Question 22

Which kinase is activated when cGMP binds to regultory domain?

Answer 22

PKG

Question 23

What happens when insulin binds to its receptor?

Answer 23

Binding of PTB (protein tyrosin) domain of the IRS to the phosphorylted tyr on the insulin receptors.

Question 24

PI3 kinase has a regultory subunit with what domain?

Answer 24

Calcium so obviousl sh2.

Question 25

Binding of TGFB (beta) to the Ser/Thr kinase receptors leads to

Answer 25

Stimulation of the oligomerization of the Type II and type I receptors.

Question 26

mutation in the EGF can result in subsitution of ala for tyr, which inhibits cell growth. What could cause it?

Answer 26

Decreased recrruitment of Grb2 to the EGF.
Which inhibits Ras, grb2 usually activates it.
Decreased PI3K, RasGaP, PLCy
PLCy can activate PKC-CaCam

Question 27

Jak is

Answer 27

A tyr kinase
Jak phosphoryltes cytokine receptors (itself) jak phosphoryltes stat proteins
Jak can be activated when cytokines bind to their receptors.

Question 28

Ligand gated ion channel receptrs bind to this and opens and ions can flow down concentraiton gradient.

Answer 28

Acetlcholine.