Cell signalling and cancer Flashcards
What kind of signalling molecules can bind to intracellular receptors?
Small, hydrophobic molecules that can pass through the membrane e.g. steroids / hormones
What kind of signalling molecules can bind to extracellular receptors?
Hydrophilic proteins e.g. insulin
What happens once a molecule has bound to an extracellular receptor?
It induces an intracellular signal transduction to alter target proteins for metabolism, gene expression and structure.
What is a receptor Tyrosine Kinase?
Enzyme-coupled receptor on the cell surface, that spans the membrane once.
The extracellular domain may vary
The intracellular domain is a cytoplasmic TK.
What does TK do?
TK phosphorylates tyrosine (Tyr) residues by catalysing the transfer of a terminal phosphate group from ATP onto self ser, Thr or Tyr.
Give 3 examples of signalling proteins that will activate RTK?
EGF, Insulin, PDGF
What pathway is used by RTK?
MAP kinases pathway (mitogen activated)
PI3-kinase pathway (Phosphatidylinositol)
What does TK activity result in?
Either activates or inhibits the target protein.
Is phosphate addition reversible?
Yes with phosphatases
What happens when a signalling molecule binds to RTK?
Induces receptor DIMERISATION. The TK domains then cross-phosphorylate each other at multiple points for AUTOPHOSPHORYLATION.
What does the phosphorylation of Tyr residues allow?
Creates a high affinity binding site for cytoplasmic proteins such as:
Grb-2 for MAP kinase pathway
PI3-kinase
What induces the MAP kinase pathway? What does the pathway result in?
GF
GROWTH and PROLIFERATION
Give the overall order of the proteins involved in MAP kinase pathway.
Signalling molecule —> RTK —> Grb-2 —> Ras —> Raf —> Mek —> Erk = Cell GROWTH and PROLIFERATION
What is Grb-2?
A GF receptor bound protein. It has a SH2 domain that can recognise phosphorylated Tyr residues on RTK. The SH3 domain binds to Sos through its proline rich motif.
What results from the formation of receptor - Grb2 - Sos complex?
Recruits and activates Ras.
What is Ras?
A G protein with intrinsic GTPase activity. It is an oncogene attached to the plasma membrane.
What is Sos?
GEF - guanine nucleotide exchange factor that activates Ras by stimulating it to exchange GDP for GTP.
What inactivates Ras?
GAPs - GTPase activating proteins stimulate Ras’ intrinsic activity to hydrolyse GTP to GDP.