BCH3042 Lecture 12: Ras and MAPK Pathway
25 May 2018
School
Department
Course
Professor
Lecture 12 – Ras and MAPK Pathway
Ras
• Monomeric small GTP binding protein → key regulator of cell growth in all
eukaryotic cells
• Relay signals from receptor tyrosine kinases to nucleus to stimulate cell
proliferation
• Biological activity of Ras is controlled by a regulated cycle of GDP/GTP
binding
• Anchored to inner side of plasma membrane –
covalent attached fatty acid
o Essential for oncogenic Ras signalling
• Mutations in Ras occur in human tumours (30%)
• Functions as switches
o On → GTP bound state
o Off → GDP bound state (resting state)
• GTP → GDP
o Input: GAP proteins
o Output: Phosphate
• GEF is needed to activate Ras s
• Proteins that regulate Ras activity
o GTPase proteins (GAPS) inactivate Ras
▪ Increased hydrolysis of GTP-bound Ras forming GDP bound
Ras
o Guanine nucleotide exchange factors (GEFs) stimulate formation of
GTP-bound Ras
• Receptor tyrosine kinase
o Tyrosine residues are docking sites for signalling proteins
o Proteins dock onto phosphorylated proteins by SH2 domains
▪ E.g. Grb-2 adaptor protein
▪ SH3 domain interacts with Ras GEF → stimulates Ras by
giving it GTP → active
Ras Activates Down Stream Signalling
Cascades
• Ras is in Map Kinase pathway
• Activation of receptor tyroskine kinase
→ activates Ras → Map Kinases
• Both receptor tyrosine kinase
activation are short lived signals
Map (mitogen activated protein)s Kinase Pathway
• Short lived signals are converted into sustained signals: relayed to nucleus to
alter gene expression
• Ras stimulates series of serine threonine phosphorylation events – longer lived
signals
• MAP kinase is core module and last in cascade
• Raf phosphorylates Mek → Mek phosphorylates Erk → phosphorylates
different proteins in cytosol
find more resources at oneclass.com
find more resources at oneclass.com
