Cell Cycle Checkpoints & Growth Factor Signaling - Quick Reference

Checkpoints in the Cell Cycle

Checkpoints ensure progression only when conditions are favorable: G1/S, G2/M, and the M (metaphase-to-anaphase) checkpoint.
Cell cycle structure:
- Interphase: G1, ext{ }S, ext{ }G2
- Mitosis: Prophase, Metaphase, Anaphase, Telophase + Cytokinesis as part of the M phase.

Proto-oncogenes: genes that promote proliferation and progression.
Tumor suppressor genes: brakes that inhibit progression when DNA is damaged or not ready.

Growth factors examples: Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF).
Receptors: G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).
Growth factors trigger signaling to drive proliferation.

Ligand binding to a GPCR (often Gq): GDP → GTP on G{ ext{q}} → receptor activation.
Effector: Phospholipase C (PLC) activated by G_{ ext{q}}.
PLC action: PIP2 ightarrow DAG + IP3.
DAG activates Protein Kinase C PKC; IP_3 increases cytosolic Ca^{2+} (from storage).
Ca^{2+} binds Calmodulin; Ca^{2+}-Calmodulin activates kinases or transcription factors, promoting proto-oncogene expression.
Overall: signals lead to transcriptional activation and proliferation.

Growth factor binding causes RTK dimerization and autophosphorylation.
Adaptor protein GRB2 links the receptor to downstream signaling.
Result: activation of transcriptional programs that promote cell cycle progression.

Proliferation is controlled by a balance between proto-oncogenes (promote) and tumor suppressor genes (inhibit).
Growth factors via GPCR and RTK pathways drive progression through the cell cycle by activating transcription factors and gene programs.
Key phosphorylation and second messenger steps include PIP2 ightarrow DAG + IP3, activation of PKC, and Ca^{2+}-dependent signaling.