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Understanding Signal Transduction Pathways

Mar 20, 2025

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Signal Transduction Lecture Notes

Introduction

  • Signal Transduction: High-yield topic in biochemistry and immunology.
  • Importance:
    • Clinically significant in various fields: biochemistry, endocrinology, neurology, neuroscience, psychiatry.
    • High-yield for USMLE and COMLEX exams.
    • Commonly avoided by students but crucial for understanding bodily communication mechanisms.

G Protein-Coupled Receptors (GPCRs)

  • Structure:
    • Located in the plasma membrane with a 7-transmembrane domain.
    • Associated with a heterotrimeric G protein (gamma, alpha, beta subunits).
  • Mechanism:
    • Signal binds to receptor; causes conformational change.
    • Alpha subunit dissociates, GDP converts to GTP, activating the alpha subunit.
  • Subtypes:
    • G<sub>s</sub>:
      • Activates adenylyl cyclase.
      • Converts ATP to cAMP.
      • cAMP activates Protein Kinase A (PKA).
    • G<sub>i</sub>:
      • Inhibits adenylyl cyclase, preventing cAMP and PKA activation.
    • G<sub>q</sub>:
      • Activates phospholipase C.
      • Converts PIP<sub>2</sub> to IP<sub>3</sub> and DAG.
      • IP<sub>3</sub> releases calcium from ER; DAG activates Protein Kinase C (PKC).

Mnemonic for GPCRs

  • AC for craps and poker:
    • A: Adenylyl Cyclase
    • C: cAMP
    • P: Protein Kinase A

Endocrine Hormones

  • cAMP Pathway: FSH, LH, ACTH, TSH, CRH, HCG, ADH (V2), MSH, PTH, Calcitonin, GHRH, Glucagon, Histamine (H2).
  • IP3 Pathway: GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1), Angiotensin II, Gastrin.

Receptor Tyrosine Kinases (RTKs)

  • Characteristics: Largest class of signal transducers, inherent enzyme activity.
  • Mechanism:
    • Growth factors bind, leading to dimerization and cross-phosphorylation.
    • Ras-GDP exchanges for GTP; activates MAP kinase cascade (Raf, MEK, ERK).
  • Mnemonic:
    • RTK stands for Ras III kinases:
    • R: Ras
    • T: Three (3 Kinases)
    • K: Kinase

Endocrine Hormones

  • Insulin, IGF-1, FGF, PDGF, EGF

cGMP Pathway

  • Mechanism:
    • Nitric Oxide activates guanylate cyclase.
    • GTP converts to cGMP.
    • cGMP activates Protein Kinase G (PKG).
  • Endocrine Hormones: BNP, ANP, EDHF.
  • Function: Significant effects on smooth muscle for vasodilation.

Conclusion

  • Mnemonics and big-picture understanding are key to mastering signal transduction pathways.
  • Remember the specific pathways and associated endocrine hormones as they are high-yield for exams.

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