Cell Signalling Flashcards
What domains do receptor tyrosine kinases have?
Extracellular, transmembrane and cytoplasmic
what is the cytoplasmic domain characterised by?
Enzyme tyrosine kinase which transfers phosphates
What happens after dimerisation of the RTKs?
Conformational change which leads to widespread phosphorylation through the tyrosines.
Give two examples of domains which can interact with the phosphorylated tyrosine residue
- SH2 (found in 100+ proteins)
2. PH domain which allows binding to phosphorylated inoside lipids as a recruitment molecule to membranes
What is ras?
A small monomeric G protein which is exists in a GTP and a GDP bound form?
Which form of Ras is the activated form and what is the molecule which activates it?
GTP - ON
GDP - OFF
GTP –> GDP by GAP (rapid hydrolysis)
GDP –> GTP by GEF
What does the GTP-bound form of ras switch on?
Serine-threonine kinase (Raf) cascade
What are Hot-spot regions within the transmembrane domain of RTKs?
Areas of mutation where the kinase activity is deregulated. For example a val-glu change strengthens the dimerised form so it is constitutively active
What is v-EGF?
Viral EFG - lacks ligand binding domain so it is constitutively active
What is Herceptin?
A biologic antibody which binds Her2 (causes breast cancers) and prevents signalling which reduces the rate of cell proliferation.
What is IRS?
Insulin receptor substrate protein, acts as an adaptor protein for linking the receptor to its downstream signalling pathway.
What do IRS activate?
PI3K cascade - converts PIP2 to PIP3
What is autoregulation?
Downstream enxymes inhibit upstream elements in the same pathway (feedback inhibition)
What are unregulated receptor pathways?
Molecular signals that inhibit insulin signalling
What is the serine phosphorylated state?
Off
