2) When Signalling Goes Wrong (Cancer) Flashcards
What is a tumour supressor gene?
p53
What typeof virus is Rous Sarcoma Virus
Retrovirus, hence why c-src and vsrc and homologous.
What is proto-oncogene (cSrc)?
describes cellular version of retroviral transforming gene.
could be mutationally altered to drive cancer.
What are the 3 major domains of Src (proto-oncoprotein)?
2 protein-protein domains, SH2 domain on Src.
What happens in the SH2 domain?
Interacts with tyrosine phosphorylated residue of C-terminal tail of Src
What conformation does Src have when inactive?
folded up tightly
What does SH3 mediate?
protein/protein interactions
What does SH3 bind to?
bind to stretches of amino acids rich in prolenes.
Activation of Src?
P removed from C-terminal tail tyrosine motif. The Src is phosphorylated, active stricture = open
v-Src C-terminal difference compared to c-Src?
1) v-Src has lost a key inhibitory C-terminal phosphorylation site –> cant form inactive conformation.
1) cSrc has a C-terminal, control catalytic activity.
What is the effect of a mutation in the SH3 domain in vSrc?
interupt the ability of SH3 domain to form compact 3D form.
In mutated form of vSrc what can SH3 domain no longer do?
prevent SH3 to prolene rich domains
What is the mutated signalling process in Noonan and Tiger syndrome?
MAP-Kinase signalling
What kind of receptor is used in Tiger syndrome?
Kinase-linked Receptor (RTK)
Does Kinase-linked receptor have an intrinsic tyrosine domain?
YES
How is a docking site created on receptor?
The Tyrosine K domain phosphorylates conserved tyrosine residues within the cytoplasmic domain on the receptor.
what binds to the docking site?
Adapter molecule Grb2
What domain does Gbr2 have that allows it to bind to docking site?
SH2 domain, bind to Tyr phosphorylated motifs.
What does Gbr2 recruit and bind to?
Signalling protein sos
What activates Ras?
When sos binds to Gbr2
How is Ras activated?
Guanine nucleotide exchange factor (GEF)
ADP –> ATP
What is the first component activated by Ras in a MAP signalling cascade?
Raf
What is the second component activated by Ras in a MAP signalling cascade?
MEK
What is the third component activated by Ras in a MAP signalling cascade?
ERK (translocate to nucleus)