title: Axl-dependent signalling: a clinical update.
abstract: Axl is a receptor tyrosine kinase that was originally cloned from cancer cells. Axl belongs to the TAM (Tyro3, Axl and Mertk) family of receptor tyrosine kinases. Gas6 (growth-arrest-specific protein 6) is a ligand for Axl. Activation of Axl protects cells from apoptosis, and increases migration, aggregation and growth through multiple downstream pathways. Up-regulation of the Gas6/Axl pathway is more evident in pathological conditions compared with normal physiology. Recent advances in Axl receptor biology are summarized in the present review. The emphasis is given to translational aspects of Axl-dependent signalling under pathological conditions. In particular, inhibition of Axl reduces tumorigenesis and prevents metastasis as well. Axl-dependent signals are important for the progression of cardiovascular diseases. In contrast, deficiency of Axl in innate immune cells contributes to the pathogenesis of autoimmune disorders. Current challenges in Axl biology are related to the functional interactions of Axl with other members of the TAM family or other tyrosine kinases, mechanisms of ligand-independent activation, inactivation of the receptor and cell-cell interactions (with respect to immune cells) in chronic diseases.
authors.affiliation: Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Slava_Korshunov@URMC.rochester.edu
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Korshunov
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human