====== 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.

===== General Information =====
  * **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

===== Functions =====
  * 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 the Central Nervous System =====
  * 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

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

===== Therapeutic Targeting =====
  * **Fostamatinib**: FDA-approved SYK inhibitor (for chronic ITP)
  * Clinical trials for:
    * Autoimmunity
    * Cancer
    * Neuroinflammation

===== SYK Signaling Pathway (Simplified) =====
  - Receptor activation (e.g., TREM1)
  - ↓ ITAM phosphorylation
  - ↓ SYK recruitment and activation
  - ↓ Downstream signals:
    * **PDK1 → STAT3** (proinflammatory transcription)
    * **PI3K–AKT** (cell survival, metabolism)
    * **NF-κB** (cytokine expression)