Cellular Proliferation & Survival

Cells and Immunity
Week 3
Dr. Mike Fry
Pathways regulating cell proliferation and survival


Coincidence detection; [Harvey McMahon];
Signal 1 + Signal 2  Logic Gate  Response [need both signal]
PTK [protein tyrosine kinase] activates RAS MAP pathway alone = partial, weak cell
division // strong apoptosis
PTK activates PI3-kinase [PKB/Akt] = produces a weak cell division signal but a strong cell
survival.
Putting both sequences together and the apoptosis
cancels out the cell survival and it produces a strong
cell division sequence.
Signalling Proliferation;
- G1: rounds of cell division [checkpoints]
- S: DNA replication
- G2: Checkpoints
- Mitosis: division


Ras MAP pathway:
1. Receptor ptk coupled to protein with functional
domains to ras switch
2. Ras GDP [off state]  Ras GTP [on state] 
Raf  Mek  MAPK  Phosphorylates
transcription factors [c-Fos / c-Jun]
- Receptors become phosphorylated upon ligand
binding
Phosphorylation:
- Enzyme mediated transfer of phosphate group
[PO42-] from ATP to another molecule species
[mediated by kinase enzymes]
- Removal of phosphate catalysed by
phosphatases enzyme family.
Protein Kinase Families;
1. Protein Serine/ Threonine kinases [1433
recognise phosphoserine / phosophothreonine, conforms protein, addition of -ve
charge [repel] active/inactive.
2. Protein Tyrosine kinases [SH2/SH3/PH/PTB]