Makindo Medical Notes

🧬 Tyrosine Kinase Receptors (RTKs) are cell surface receptors that control growth, differentiation, metabolism, and survival. They are activated by growth factors, triggering powerful intracellular signalling cascades. RTKs are central in health 🌱 and disease ⚠️, especially cancer.

🏗️ Structure of Tyrosine Kinase Receptors

• Extracellular Domain 🧲 :
  • Ligand-binding site for growth factors.
  • Ensures signal specificity.
• Transmembrane Domain 🧱 :
  • Single α-helix spanning the membrane.
• Intracellular Domain ⚡ :
  • Tyrosine kinase enzymatic site.
  • Phosphorylates tyrosine residues → activates signalling proteins.

⚙️ Functions of RTKs

• 📈 Regulate cell growth & differentiation
• 🔥 Control metabolism
• 📡 Mediate responses to extracellular signals
• 🏗️ Maintain tissue & organ development

🔑 Activation Mechanism

• 🎯 Ligand Binding → growth factor attaches to extracellular domain.
• 🤝 Dimerization → two receptors pair together.
• 💥 Autophosphorylation → each receptor phosphorylates its partner.
• 📡 Signal Transduction → phosphorylated tyrosines act as docking sites → downstream cascades (MAPK, PI3K/Akt, etc.).

🏥 Clinical Significance

• 🦀 Cancer :
  • Mutations/overexpression drive uncontrolled growth.
  • Targeted therapies: EGFR inhibitors (lung Ca), HER2 inhibitors (breast Ca).
• 👶 Developmental Disorders :
  • RTK gene mutations → congenital abnormalities.
• ❤️ Cardiovascular Disease :
  • RTKs regulate vascular tone & angiogenesis; dysregulation worsens atherosclerosis & hypertension.

📌 Key Examples

• EGFR 🧲 : cell growth & proliferation → mutated in lung/colorectal cancer.
• VEGFR 🌱 : drives angiogenesis → target in anti-cancer therapy.
• PDGFR 🫀 : regulates vascular/cardiac growth → linked to atherosclerosis & malignancy.
• Insulin Receptor (IR) 🍬 : essential for glucose uptake → impaired in diabetes.

📖 Summary: RTKs act as “growth switches” on the cell surface. When ligands bind → dimerization & phosphorylation → major signalling cascades. They are essential for development, but when dysregulated, they drive cancer and other diseases. 🎯