Exam 4 (2) Flashcards
What pathway governs the G1 to S transition?
Mitogen-Induced DNA Replication –> Ras - MAP Kinase Pathway followed by a Cyclin Pathway
What are the 5 steps for the pathway that governs the G1 to S transition?
Mitogen-Induced DNA Replication –> Ras - MAP Kinase Pathway followed by a Cyclin Pathway
- Mitogen binds to a membrane receptor –> phosphorylates Ras
- Ras activates MAP Kinase, leading to the synthesis of Myc (transcription regulatory protein)
- Resulting Proteins phosphorylate CyclinD-CDK4
- CyclinD-CDK4 phosphorylates Rb –> releases E2F (transcription factor)
- Transcription –> DNA Synthesis
How do Cyclin Dependent Kinases (CDKs) exist in their active form?
CDKs (catalytic subunit) form pairs with their corresponding Cyclins (regulatory subunit)
What happens to Cyclin Dependent Kinases in their active form?
They are phosphorylated and can now do the job of a typical kinase (phosphorylate other proteins!)
Dynamics of the Concentrations of Cyclin Dependent Kinases and Cyclins in Cells/Organisms
The concentration of CDKs is constant
The concentration of the required associated cyclins changes throughout each phase of the cell cycle (some organisms only need 1 CDK for multiple processes; others have CDKs for each transition point)
2 Steps to get to an Active Cyclin Dependent Kinase
- The corresponding cyclin binds to the CDK –> induces conformational change of the T-loop of the CDK
- Thr residue of said T-loop is then phosphorylated by a CDK-activating kinase (CAK) –> induces a second conformational change that makes the T-loop accessible to substrates (FULLY ACTIVATED)
3 External Regulatory Elements for Active Cyclin Dependent Kinases
- Wee1 Kinase: phosphorylates a different site of the CDK (relative to CAK) –> renders inactive
- Cdc25: dephosphorylates site targeted by Wee1 –> reactivates
- CDK inhibitors (CKIs) physically bind to cause structural rearrangement –> renders inactive
