Axl

Axl is a TAM receptor tyrosine kinase activated by GAS6, and TAM receptors support apoptotic-cell recognition, efferocytosis, immune regulation, tissue homeostasis, and cancer-related signaling^[1][2]. Mechanistically, Axl participates in ligand-induced TAM activation with TYRO3 and MERTK, but each receptor shows distinct activation patterns with GAS6, PROS1, apoptotic cells, phosphatidylserine vesicles, and enveloped virus^[3]. In cancer models, Axl activation stimulates MAPK, AKT, and FAK pathways, while Axl inhibition or knockdown reduces tumor growth, migration, colony formation, and chemoresistance in NSCLC and neuroblastoma^[4][5]. In inflammatory disease models, AXL/MERTK inhibition protected against pancreatic necrosis by limiting CXCL2-related neutrophil infiltration, whereas soluble Axl increased in lupus nephritis and multiple sclerosis lesions, indicating disease-linked dysregulation of GAS6-TAM signaling^[6][7][8]. Compared with MERTK, Axl showed stronger effects on chemosensitivity in NSCLC, distinct ligand-response behavior among TAM isoforms, and critical roles with TYRO3 in GPVI-mediated platelet activation^[3][4][9]. For experimental applications, Axl inhibitors, soluble TAM domains, and antagonist or agonist antibodies provide tools to test TAM signaling, immune regulation, apoptosis, and therapeutic sensitization^[3][6][10].