Cell Sigs Flashcards
(28 cards)
Cam Kinase II
Calcim calmodulin binds regulatory part of CamKII, conformational change = autophosphorylate, remain active.
How to inactivate CamKII?
Phosphatase activity
Visual cycle
Turn on
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.
Visual cycle
Turn off
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).
How does cell membrane guanylate cyclase receptor work? Gcap
Ligand binding extracell domain Nlinked glycosylation.
Binds ANP.
Increased cGMP+activated PKC.
Hypovolemia, hypotension.
Inhibits Na+ reabsorption
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Atp allosteric activates for conform change, affinity for receptor ligand decreases afterwards.
Dephosphoryla1tion makes receptor inactive
Recycing of GCAP
Following isomerization and rlease from opsin protein
All trans retinal reduced to all trans retinol.
Travel back to retinal pigment epithelium .
Esterified by lecithin retinol transferae
Stored as retinyl ester.
What is TGFB receptor and what is its purpose?
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).
ISMaD
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.
MH-I
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
MH2
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.
C-I
Dag binding domain containing pseudosubstrate that PKC binds and is inactive rendered.
JaK homogly domains
Socs box promotes degradation via interaction with proteasomes.
always in C termini
MEK = dual specific kinase, phosphoryltes Thr and TYR residues. Most kinases are either ser Thr or ser TYR.
aKT=PKB
1
JaKstat
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.
How does socs work
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.
1G protein coupled receptors are desensitized
Via phosphorylation by G protein coupled receptor kinases.
Pertussis toxin prevents activation of
Galpa(a) and dimer protein
Role of PLC
Results in activateion of PKC and calcium calmodulin kinase.
Protein kinase C PKC in its inactive form has?
A. Pseudosubstrate domain occypying its substrate binding site.
Absoprtion of light by rhodposin leads to
Close of cGMP dependent soium calcium channels.
Name the binding partners of SH2 PTP SH3 PH C2
SH2 Tyr residues phosphorylated Also phosphorylted tyr’s SH3 prolines PH PI C2 calcium
What happens to blood pressure when you have decreased binding of aNP to receptor?
Inability to decrease blood pressure, hypertension, may be due to mutation of kinase hhomogy domains.
Which kinase is activated when cGMP binds to regultory domain?
PKG
What happens when insulin binds to its receptor?
Binding of PTB (protein tyrosin) domain of the IRS to the phosphorylted tyr on the insulin receptors.
PI3 kinase has a regultory subunit with what domain?
Calcium so obviousl sh2.
