Lecture notes from Imperial College London, Medical Biosciences, 2nd year, Cancer Biology (CBIO) module
A crucial characteristic of every living cell is its ability to communicate with neighbouring cells. This interchange of information between a cell and its environment is what is known as cell...
Cell Signalling in Cancer
- cell signalling by membrane-bound receptors to allow neighbouring cells to communicate
=> response to environmental signals => preserve position & coordination of tissues
=> cell signalling pathways: regulate growth, proliferation, survival... -
What do the receptor tyrosine kinases look like?
- transmembrane p: 1) cytosolic (intracellular) region: RTK receptor tail which functions as a
tyrosine kinase 2) extracellular region: ligand binding site
- there are 20 RTK subfamilies with ≠ domains:
=> ErbB family:
=> receptors activated by epidermal GF
family (disulphide bonds determine specificity)
=> immunoglobulin-like domains
=> heparin-binding sites
=> glycosylation sites
=> EGFR (ErbB-1): mutated in cancers
=> ErbB2 act as a coreceptor for others
(HER2)
signalling proteins:
- cytosolic signalling p bind to docking sites
=> SH2 domain => bind the phospho tyrosine
(Y) on RTKs (affinity for specific aa seq)
=> bind simultaneously => several pathways
=> SH3 => bind & recruit to RTK p w/ proline
position of tyrosine
residues & unique docking Adaptor proteins: contain only SH3 and => bind receptor tail directly/ via adaptor p
sites (aa sequence) SH2 + lack catalytic domains (kinase, GAP, PLC...)
- signalling p propagate the GF signal => alter gene transcription
=> crosstalk bw ≠ intermediates in signalling pathways
- Shc (transforming p 1) & Grb2 (GF receptor-bound p 2): adaptor p for signal transduction/ cell com
- adaptor proteins link receptors to signalling pathway BUT don’t have an intrinsic signalling ability
, Mutations causing cancer affect signalling pathways
- aberrant signalling => escape normal control mechanisms => target for cancer chemotherapy
- oncogenic mutations of signalling p: overexpressed/ make abnormal p
=> include RTKs, EGFR, Ras, RAF, Akt, SRC, Abl, lipid kinases, estrogen receptor, Myc, cyclin..
=> deletions of tumour suppressors: p53, PTEN (negative regulator of the P13K-Akt pathway)
- RTKs: enzymatic activity in their polypeptide chain triggered by growth factors & some hormones
=> adjacent RTKs join with each other: cross-linked dimers produced locally in low conc
=> tyrosine kinase activity: cross-phosphorylation (RTK phospho tyrosine residues on the other)
④
P
membrane receptor
r cell sig.
1) receptiono
2) transduction
d
3) responseu(cellular activity,
activationc gene...)
e
Ras activation
-
d
- binding of a GF to an RTK => Ras activation l
o
=> membrane-bound GTP/ GDP-binding (G) protein => acts as a ‘molecular switch’
c
adaptor p Grb2 SH2 domain bindsa a
l 2
phosphotyrosine docking site and the
SH3 domains recuit Sos l
y
i
- Sos: guanine nucleotide exchange protein (GEF) n
=> GEF aids separation of GDP from Ras l
=> GTP spontaneously binds to Ras & GEF detaches o
=> GAP hydrolyses GTP to restore inactive GDP w
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller lisaribau. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £7.99. You're not tied to anything after your purchase.
