SYK (Spleen Tyrosine Kinase)

SYK is a cytoplasmic tyrosine kinase involved in innate and adaptive immune signaling. It plays a critical role in the activation of immune cells such as B cells, macrophages, microglia, and mast cells.

• Full name: Spleen Tyrosine Kinase
• Gene: SYK (Chromosome 9)
• Protein type: Non-receptor tyrosine kinase
• Location: Cytoplasm
• Expressed in:
  • B cells
  • Myeloid cells (e.g., macrophages, microglia, dendritic cells)
  • Mast cells
  • Platelets

• Transduces signals from ITAM-bearing receptors such as:
  • B Cell Receptor (BCR)
  • Fc receptors (FcγR, FcεR)
  • TREM1 (via DAP12 adaptor)
• Activates key intracellular signaling pathways:
  • PI3K/AKT
  • MAPK/ERK
  • NF-κB
  • PDK1 → STAT3

• In microglia, SYK mediates:
  • Inflammatory activation
  • Cytokine release
  • Phagocytosis
• In glioblastoma (GBM):
  • Activated via TREM1 on microglia
  • Promotes tumor-supportive immune environment via SYK–PDK–STAT3 axis

• Autoimmune disorders: rheumatoid arthritis, lupus
• B-cell malignancies: lymphomas
• CNS disorders:
  • Glioblastoma progression
  • Alzheimer's disease (via microglial dysfunction)
• Allergy: mast cell degranulation

• Fostamatinib: FDA-approved SYK inhibitor (for chronic ITP)
• Clinical trials for:
  • Autoimmunity
  • Cancer
  • Neuroinflammation

1. Receptor activation (e.g., TREM1)
2. ↓ ITAM phosphorylation
3. ↓ SYK recruitment and activation
4. ↓ Downstream signals:
   • PDK1 → STAT3 (proinflammatory transcription)
   • PI3K–AKT (cell survival, metabolism)
   • NF-κB (cytokine expression)