Signal Transduction Pathways

Signal Transduction Pathways - Cellular Chatterbox Basics

• Core Idea: Cells interpret external signals to trigger internal responses.
• Key Players & Steps:
  • Ligand: The initial signal molecule (e.g., hormone, growth factor).
  • Receptor: Protein that binds the ligand; ensures specificity.
  • Second Messenger: Intracellular molecules (e.g., cAMP, Ca²⁺, IP₃, DAG) that relay and amplify the signal.
  • Effector Protein: Executes the cellular response (e.g., enzyme, transcription factor).
• Fundamental Processes:
  • Signal Amplification: A few ligands activate many downstream molecules.
  • Integration: Cells combine multiple signals for a unified response.

⭐ Signal amplification allows a small number of ligand-receptor interactions to evoke a large cellular response, crucial for physiological sensitivity.

Signal Transduction Pathways - Cell's Doorkeepers

Signal Transduction Pathways - Intracellular Highways

Core intracellular cascades converting receptor signals into cellular actions:

• cAMP Pathway (GPCRs):
  • Gs: Activates Adenylyl Cyclase ($ATP \rightarrow cAMP$). Gi: Inhibits it.
  • cAMP (2nd messenger) $\rightarrow$ PKA activation $\rightarrow$ protein phosphorylation (e.g., glycogenolysis enzymes).
• Phospholipase C (PLC) Pathway (GPCRs):
  • Gq: Activates PLC.
  • PLC: $PIP_2 \rightarrow IP_3 + DAG$ (2nd messengers).
  • $IP_3 \rightarrow Ca^{2+}$ release (ER). $DAG + Ca^{2+} \rightarrow$ PKC activation (e.g., smooth muscle contraction).
• MAPK/ERK Pathway (RTKs):
  • RTK activation (growth factors) $\rightarrow$ Ras (small G-protein) on.
  • Ras $\rightarrow$ Raf $\rightarrow$ MEK $\rightarrow$ ERK (kinase cascade).
  • ERK $\rightarrow$ nucleus $\rightarrow$ gene expression (proliferation, differentiation).
• JAK-STAT Pathway (Cytokine Receptors):
  • Cytokine binding $\rightarrow$ JAK activation.
  • JAKs phosphorylate STATs.
  • STATs dimerize $\rightarrow$ nucleus $\rightarrow$ gene transcription (inflammation, immunity).

📌 Mnemonic (G-proteins): QISS - Gq: PLC $\uparrow$ ($IP_3, DAG \uparrow$) - Gi: AC $\downarrow$ (cAMP $\downarrow$) - Gs: AC $\uparrow$ (cAMP $\uparrow$)

cAMP Pathway:

⭐ The Ras-MAPK pathway is vital for cell growth/differentiation; its dysregulation is frequent in cancers.

Signal Transduction Pathways - Control & Disease Links

• Control Mechanisms:
  • Receptor Desensitization: Homologous/Heterologous.
  • Receptor Regulation: Downregulation (↓ receptors), Upregulation (↑ receptors).
  • Signal Termination: GTPase activity, phosphodiesterases (PDEs break down $cAMP$/$cGMP$).
  • Cross-talk: Pathway integration.
• Clinical Relevance:
  • Cholera Toxin: Locks Gs active → ↑ $cAMP$.
  • Pertussis Toxin: Inhibits Gi → ↑ $cAMP$.
  • Insulin Resistance: Impaired insulin signaling.
  • Beta-blockers: Receptor antagonists.
  • Viagra (Sildenafil): PDE5 inhibitor → ↑ $cGMP$.

⭐ Cholera toxin ADP-ribosylates the Gsα subunit, locking it in an active state, leading to continuous cAMP production and severe diarrhea.

High‑Yield Points - ⚡ Biggest Takeaways

• GPCRs, the largest family, use G proteins (Gs, Gi, Gq) and second messengers like cAMP, IP3, DAG.
• Receptor Tyrosine Kinases (RTKs) (e.g., insulin receptor) dimerize and autophosphorylate.
• JAK-STAT pathway mediates cytokine signaling using associated tyrosine kinases.
• Nitric Oxide (NO) activates guanylyl cyclase, increasing cGMP for vasodilation.
• Calcium (Ca2+) is a key second messenger, released via IP3-gated channels.
• Signal termination involves phosphodiesterases (cAMP/cGMP) and phosphatases.