Tyrosine-protein kinase receptor AXL (AXL)

Tyrosine-protein kinase receptor AXL is a cell surface **receptor tyrosine kinase** that belongs to the **TAM family**—comprising Tyro3, Axl, and Mer. It features two immunoglobulin-like domains plus two fibronectin type III domains extracellularly. Its primary ligand is growth arrest-specific protein GAS6—a vitamin K-dependent factor—which activates the receptor by promoting dimerization. Upon activation by GAS6 binding, **AXL transduces signals through key pathways including PI3K-AKT-mTOR**, MEKERK, NF-kB, and JAK/STAT. These cascades regulate diverse cellular processes such as proliferation, migration/invasion/metastasis formation via epithelial-to-mesenchymal transition (EMT), survival via anti-apoptotic mechanisms, angiogenesis promotion within tumors, stemness maintenance in cancer cells—and crucially—modulation/suppression of innate immunity by limiting dendritic cell maturation/functionality. AXL overexpression has been strongly linked to aggressive tumor behavior across multiple solid tumors—including triple-negative breast cancer (**TNBC**), non-small-cell lung cancer (**NSCLC**), acute myeloid leukemia (**AML**), pancreatic cancer—and correlates with poor patient outcomes. It also plays a role in acquired drug resistance through EMT induction or direct crosstalk with other RTKs like EGFR. In normal physiology it contributes to efficient clearance of apoptotic debris (“efferocytosis”) by phagocytes such as macrophages/dendritic cells while suppressing excessive inflammatory responses. Therapeutic targeting strategies focus on small molecule inhibitors blocking its catalytic activity or antibodies disrupting ligand-receptor interactions; however safety concerns arise from its essential roles outside malignancy—particularly regarding immune homeostasis.[2][5][1][4]

Other names

Axl receptor tyrosine kinaseUFO (historical gene name)AXL receptor tyrosine kinaseTyro7 (less common)TAM family member (with Tyro3 and Mer)

Small molecule inhibition of the intracellular tyrosine kinase domain to block downstream signaling pathways such as PI3K-AKT-mTOR, MEK/ERK, NF-kB, JAK/STAT. - Antibody-mediated blockade of ligand binding or receptor dimerization. - Disruption of Gas6–AXL interaction to prevent activation.