Signal Transduction Overview

Introduction

• Signal transduction is a significant topic in biochemistry and immunology.
• It's crucial for understanding various bodily systems and is a high-yield topic for exams like USMLE or COMLEX.
• Many students find it challenging, but grasping it can earn 'free points' on exams.

G-Protein-Coupled Receptors (GPCR)

• Integral for numerous physiological processes.
• Structure: Located within the plasma membrane, featuring a receptor with a seven-transmembrane domain.
• Components:
  • Receptor: Binds signals on the extracellular side.
  • G-Protein Network: Composed of alpha, beta, and gamma subunits (heterotrimeric).
    • Activation:
      • Signal binding causes conformational change.
      • GDP on alpha subunit is converted to GTP, activating the alpha subunit.

G-Protein Subtypes

• G_s (Stimulating): Activates adenylyl cyclase → Converts ATP to cAMP → Activates protein kinase A (PKA).
  • Mnemonic: Go to "AC for Craps and Poker"
  • Endocrine hormones influenced: FSH, LH, ACTH, TSH, CRH, HCG, ADH (V2 receptor), MSH, PTH, Calcitonin, GHRH, Glucagon, Histamine (H2 receptor).
• G_i (Inhibitory): Inhibits adenylyl cyclase, preventing cAMP formation, thus inhibiting PKA activation.
• G_q (Activating): Activates phospholipase C → Converts PIP2 to IP3 and DAG.
  • Functions:
    • IP3: Releases calcium from the endoplasmic reticulum.
    • DAG: Activates protein kinase C (PKC).
  • Endocrine hormones influenced: GnRH, Oxytocin, ADH (V1 receptor), TRH, Histamine (H1 receptor), Angiotensin II, Gastrin.

Receptor Tyrosine Kinases (RTKs)

• Largest class of signal transductors with inherent enzyme activity.
• Process:
  • Binding causes dimerization and cross-phosphorylation.
  • Creates SH2 domain for further signal cascade.
  • Activated Ras → Raf → MEK → ERK pathway.
  • Mnemonic: RTK = Ras, Three Kinases (drop a kinase down the pathway).
  • Endocrine hormones influenced: Insulin, IGF-1, FGF, EGF.

cGMP Pathway

• Starts with Nitric Oxide interacting with guanylate cyclase.
• Converts GTP to cGMP → Activates protein kinase G (PKG).
• Effects: Significant in smooth muscle vasodilation.
• Endocrine Control: BNP, ANP, EDRF.

Conclusion

• Signal transduction is essential for understanding clinical pathways and examination preparation.
• Utilize mnemonics and big-picture thinking to remember pathways effectively.