Cell Signalling Flashcards
(25 cards)
are the signalling pathways induced by extracellular signals always in a straight line
no one signal can have multiple effects
or multiple signals can have the same effect
what does the release of DNA binding protein into the nucleus cause
target amplification
what are the 8 most important signalling molecules
growth factors hormones interleukins interferons chemokines extracellular matric proteins (e.g. fibrinogen) toxins (v. important, aberrant) neurotransmitters
what are the most important transmembrane receptors
GPCR cyrokine receptors RTKs (dimerise in the event of phosphorylation) TGFbeta receptors hedgehog receptors Wnt receptors notch receptors
how does relay of a signal most happen
post translational modfications (covalent changes)
what are the different modes of signal transmission
postranslational modification
protein degradation
conformational coupling (diffusion dependent complex formation)
conformational coupling (preformed complex)
what is the role of kinases
take a phosphate from ATP to make it into ADP
then transfer it to substrate
what does phosphatase do
removes phosphate from substrate
how are kinase 1,2,3 ect activated
by the phosphorylation of kinase 1
this then phosphorylates kinase 2 and so on
what amino acids are most targeted by phosphorylation
S,T and Y
what happens to the rtks tails when bound to a ligand
ligand induced transphosphorylation
expression of phosphotyrosines on the cytoplasmic tail
this attracts other signalling molecules which bind to tail and also things bound nearby in membrane (e.g. RAS)
what happens in glioblastoma
over expression of RTKs
what do monoclonal antibodies therapies do to RTKs
stop ligand binding
what do tyrosine kinase inhibitors do
inhibit action of cytoplasmic tail
4 main steps in RAS pathway GO!
RAS BRAF (dimerisation) MEK (phosphorylation) ERK (phosphorylation) =transcription
what mutation is in 50% of maligant melanomas
BRAF V600E
what does the BRAF V600E mutation do
dimerises RAF meaning it doesnt need signals from RAS
why does resistant happen e.g. BRAF inhibitors
cancer found away to go around the blockade- splice variant, NRAS mutation, CRAF overexpression, MEK mutation, COT expression
what is the best way to prevent resistance
combo therapies given for short time
what is ubiquitylation
protein substrate modified by addition of small ubiquitin(which travels through smaller enzymes in chain)
binds to substrate which causes signalling cascade to proteasome
what does the proteasome do
degrades protein that are associated with ubiquitin
how does the binding of ubiquitin affect proteasomal action
monoubquitination- DNA repair viral budding, gene expression and endocytosis
multiubiquitination- endocytosis
branched polyubiquitination chain- modulation
polyqbiquitination- proteasomal damage tolerance, degradation, signal activation, kinase activation and endocytosis, NF-Kb activation
what degrades 80% of protein in cells
the proteasome
why is the proteasome helpful to cancers
malignant cells make lots of antibodies- need proteasome to get rid of these so cancer cells can survive
