Lecture 3 - Self-sufficiency in growth signals Flashcards
Hillocks
Related pathways
unseen small hills
passenger mutations
comparison of two colorectal cancers
by large don’t show many common mutations, but do show they’re in the same pathways
Probability of getting cancer is…
proportional to the number of changes
this increases with age
Statistics show there are over….. mutations in any given cancer
over 15
Protein phosphorylation
dynamic and reversible process which changes the functionality of protein targets
Growth factor signalling pathway
growth factor binds to RTK, causes dimerisation and cross-phosphorylation
causes Grv2 to bind
Ras-Gef binds to Grb2 adaptor protein
causes GDP to GTP hydrolysis which activates Ras
causes downstream signalling
Residues 12 and 61 are….
gatekeepers for GTP binding
Guanine structure is different..
depending if GTP or GDP are bound, determines active vs. inactive
Three ways self-sufficiency might arise
Growth factor presence
Ligand-indpendent signalling
GTPase switch off failure
Growth factors and self-sufficiency
normally GF produced by another cell, but cancer cells can produce their own GF so no longer require environmental signalling
Ligand-indpendent signalling and self-sufficiency
i.e. no extracellular signalling
RTKs turn each other on without ligand binding
GTPase switch off failure in self-sufficiency
usually 2 forms - GTP or GDP bound
Ras always on with constitutive downstream signalling