Major Signaling Pathways to Study

A. GPCR–cAMP Pathway

• Ligand binds GPCR → activates Gs protein → adenylyl cyclase → ↑ cAMP → activates protein kinase A (PKA)→ phosphorylation cascade.

• Examples: Adrenaline (β-adrenergic), glucagon.

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B. GPCR–Phospholipase C (PLC) Pathway

• GPCR activates Gq protein → phospholipase C-β → cleaves PIP₂ → forms IP₃ & DAG.

• IP₃ → releases Ca²⁺ from ER; DAG + Ca²⁺ → activates PKC.

• Examples: α-adrenergic receptors.

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C. RTK–MAPK Pathway

1. Ligand (EGF, insulin) binds RTK → dimerization & autophosphorylation.

2. Adaptor proteins (Grb2, SOS) activate Ras (small GTPase).

3. Ras → Raf → MEK → ERK (MAP kinase cascade).

4. ERK enters nucleus → gene expression changes.

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D. RTK–PI3K–Akt Pathway

• RTK activates PI3K → converts PIP₂ to PIP₃.

• PIP₃ recruits Akt (PKB) → promotes cell survival & growth (inhibits apoptosis).

• Example: Insulin signaling.

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E. JAK–STAT Pathway

• Cytokine binds receptor (no intrinsic kinase activity).

• JAK (tyrosine kinase) phosphorylates receptor → recruits STAT transcription factors → gene transcription.

• Example: Interferon signaling.

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F. TGF-β/SMAD Pathway

• TGF-β binds receptor → phosphorylates SMAD proteins → SMAD complex → nucleus → transcription regulation.

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G. Wnt/β-Catenin Pathway

• Wnt binds Frizzled receptor → inhibits β-catenin degradation.

• β-catenin accumulates → moves to nucleus → activates target genes.

• Importance: Development, cancer.

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H. Hedgehog Pathway

• Hedgehog binds Patched receptor → activates Smoothened → Gli transcription factors → developmental gene expression.

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I. Notch Signaling

• Notch receptor binds ligand (on adjacent cell) → proteolytic cleavage → intracellular domain goes to nucleus → transcription changes.

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J. NF-κB Pathway

• Signal (e.g., TNF-α) → activates IKK complex → phosphorylates IκB (inhibitor) → NF-κB released → nucleus → immune/inflammatory genes.

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K. Plant Signaling Pathways

• Two-component systems: Histidine kinase → response regulator (e.g., ethylene receptor).

• Light signaling: Phytochromes (red/far-red), cryptochromes (blue light).

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