Feb 6 Flashcards
What is the guanine exchange factor for RAS?
SOS
What happens to Cdk1 and PP2A levels respectively in the cell during mitosis?
Cdk1 level is low during interphase, as PP2A deposphoryaltes it. At M phase (mitosis), PP2A level plummets, so CDK1 is PO4’d and it peaks, then once PP2A is activated then Cdk1 levels lower so exit mitosis.
How is PP2A activity lowered during mitosis to allow Cdk1 to be PO4’d?
FAM122A binds to PP2A-B55 at substrate recruting site. Then ARPP19 has a PO4 on it, it will bind at the active site, but not dePO4’d as it doesn’t have correct sequence around the PO4. Once something happens, ARPP19 loses PO4, so leaves active site of PP2A-B55.
What is the other common name for PP2B? What domains does each subunit have, function/
It is calcineurin. A subunit has catalytic domain, calmodulin binding domain, autoinhibitory domain. B subunit has EF hands to bind to Ca2+’.
When Ca2+ bound to EF hands, change conformation so calmodulin binds to its region, and now the inhibitory peptide bends out of the way of the active site.
What is NF-AT? What dephosphorylated by? Effect of drugs?
It is Nuclear Factor of Activated Transcription. Drug cyclosporin binds to cyclophilin, and now this complex has affinity for PP2B, although either of these proteins themselves don’t bind. NF-AT is dePO4’d by PP2B.
Blocking PP2B will inhibit signal cascade, no T-cell proliferation so no immune response.
How are T-cells activated, what is rough pathway?
- Macrophage will eat invader, then present it to T-cells.
- The antigen on macrophage binds to RTK.
3.Signalling cascade
4.Ca2+ released from SER
- High Ca2+ bind to EF hands, then calmodulin to its part, so PP2B now active, will dePO4 NF-AT
- Active NF-AT has nuclear import signal exposed, will go into nucleus, bind to DNA, get T-Cell proliferation
Protein phosphatase 2C is dependent on ____ and is _____meric?
It is depended on Mg2+ for activity, and is monomeric
Is PP2C related to PPP enzymes?
Completely unrelated to PPP enzymes, but similar function, convergent evolution
Transforming Growth factor B (TGFB) binds to what type of receptor kinase and binds to what do do what? What motif to bind to PO4’d serines?
It is a Ser and Thr kinase. SMAD2/3 binds to PO4’d receptor, then SMAD4 binds to the phosphates on the receptor’s serines. MH2 domain
Myotubularin targets what?
Targets phosphoinositides except PIP3
What do phosphatases look like diff in binding pocket? Tyr, DSP, Myotubularin
Protein tyrosine phosphatases (PTPs) have deep pocket, then Dual specificity phosphatases have shallower pocket. Then myotubularin targets phosphoinositides so very wide and shallow pocket to fit inositol ring.
What is special about Monosiga brevicollis?
It is the last surviving common ancestor of metazoans. It has lots of SH2 domains, RTks, PTP
What did Monosiga brevicollis change the way we think we evolved RTK’s?
At first for signalling, but this organism is unicellular, it used RTKs in different ways, u
Retroviruses carry genetic info in what form?
RNA
What % of human cancers are caused by mutant versions of RAS genes?
50%
