Switches and Cytokines Flashcards
what does EGF bind to ?
RTK (Receptor Tyrosine Kinase)
explain the EGF pathway
1) EGF binds to RTK
2) RTK auto- phosphorylates and activates cytosolic kinases
3) The kinases enter the nucleus and phopshorylates TFs
4) this leads to transcriptional activation
why is RTK different?
because it is both a receptor and a kinase and therefore when ligand binds it causes receptor dimerisation and activation of itself (the kinase)
what is difference between inactive and active RAS?
Inactive: GDP
Active: GTP
what does the SH2 domain recognise and where can it be found?
SH2 recognises phosophotyrosine (hence recognising RTK)
can be found on GRB2
what does SH3 domain recognise and where can it be found?
SH3 recognises proline rich peptides
can be found on SOS
what does phosphorylation on kinases do?
changes structure of the lip domain making them active
what are GEFs and give an example
Guanosine exchange factors
eg. SOS
What are GAPs
GTPase activating proteins
what are RGSs
Regulators of G-protein signalling
what are GDIs
Guanone nucelotide dissociation inhibitors
describe GTPases
GTP binding proteins
- around 15-25kDa
- 160-180 Amino acids
- have conserved alpha, beta topology (5a and 6b)
what are the two switches in GTPase
- G2(T) threonine is the catalyst
-G3 (DxxG)
what and where is the binding motif in GTPases
P-loop (GxxxxGKS/T)
what do matrix metalloproteinases do ?
they can mature/ release EGF from membrane proteins
what is SPR and what is it used to study?
Surface Plamon Resonance - used to study drug binding
- ligand receptor interactions
- antibody-antigen interactions
- protein-DNA interations
describe simply how SPR works?
1) solution of prey molecules (during association - creates ligand receptor binding)
2) buffer wash causes dissociation
over about 10 minutes
what deactivates CDK and how ?
Wee1 deactivates CDK by phosphorylation on tyrosine 15
what can activate CDK?
CAK activates CDK by phopshorylation on threonine 161
what is the process of CDK/ cell cycle control?
1) Wee1 deactivates CDK by phosphorylation on tyrosine 15
2) CAK can activate CDK by phosphorylation on threonine 161
3) Cdc25 activates CDK by dephosphorylation on tyrosine 15
4) CDK activation
5) Rb phosphorylation
6) E2f activation
7) autostimulation
8) Cell cycle progression
9) Further Rb Phosphorylation
