4 Cell Signalling and Cancer Flashcards
What 2 main cell signalling pathways were explored in this lecture?
Mitogen activated protein (MAP) kinase
Phosphatidylinositol (Pl) 3-kinase
What do protein kinases do?
catalyse the transfer of terminal phosphate group of ATP to Ser, Thr, or Tyr on proteins
What happens in RTK autophosphorylation?
binding of the singalling molecule causes dimerisation
kinase domains of neighbouring recepters cross phosphorylate each other
What is Grb-2?
growth factor receptor - bound protein 2
What is the SH2 domain on Grb-2 for?
recognises specific phosphorylated Tyr residues on RTKs
What does the SH3 domain on Grb-2 do?
binds to a proline rich moif in Sos (protein)
What does the assembly of the receptor - Grb-2 - Sos complex do?
enables Sos to recruit and activate Ras
How does Sos activate Ras?
stimulating it to exchange GDP for GTP
How is Ras inactivated?
GTPase activating proteins (GAPs) stimulate GTPase
How does Ras activate Raf?
by conformational change
not phosphorylation
What is the function of Erk?
phospharylation of target proteins (kinases) and gene regulatory proteins in the nucleus)
Name 5 genes activated by Erk
C-jun C-fos C-myc C-myb Cyclin D
Name 4 ways in which the MAP signal can be turned off
Removing signal
switching off activated RTK
Ras GAPs
dephosphorylation of target proteins
What might switch off the activated RTKs?
protein tyrosine phosphatases like SHP-1 and SHP-2
Give 2 examples of Ras GAPs
p120(GAP)
neurofibromin