Growth Factor Receptors Flashcards
how was EGFR characterised?
sequenced and found to be homologous to v-erbB (one of two oncogenes carried by AEV). verbB = truncated form of chicken EGFR gene ErbB1.
How do we know that PDGF signalling can be so subtle.
Use same receptor and expose to either PDGF-AA or PDGF-BB –> instances where response varied.
What is Pertuzumab and how does it function?
constitutively binds extended ErbB2 extracellular region –> prevents dimerization arm interacting with another ErbB2 or another ErbB receptor.
Inhibits neuregulin induced ErbB3 heterodimer formation.
What is the universal receptor and the universal ligand for PDGF?
R = PDGF alpha alpha L = PDGF BB
Give two examples of mutations in PDGF and their effects.
PDGF-B - translocation –> dermatocarcinoma.
PDGF-B-R - traslocation –> CML.
What mutational effects result from FGFR1?
What does thalidomide target?
amplified in breast cancer
mutated in melanoma
translocated in stem cell leukaemia.
FGF signalling and in clinical trials for adults shown to suppress tumour weight and metastasis.
Where can the majority of HGFR linked mutations be seen?
Transcriptional upregulation of MET - in ovarian, pancreatic and prostate carcinomas.
MET germline mutations seen rarely in childhood hepatocellular carcinoma.
What link can be seen between IGFRs and cancer?
IGFIR overexpressed in oestrogen receptor positive breast cancer and overexpression correlates with resistance to anti-cancer treatments.
High levels of IGF-I seen in prostate cancer.
How can c-src be made transforming?
NOT by overexpression. Mutations found, including deletion near C terminus of Tyr527. Polyoma middle T can also bind Tyr527, activates c-src. (dephosphorylation at Tyr527 inhibits signalling)
What evidence links different proto-oncogenes in a common pathway?
PDGF stimulation cause rapid increase in c-myc or c-Fos/Jun expression. Not blocked by cyclohexamide - immediate early genes.
