Disease relevance of Axl

• The Gas6/Axl system is implicated in several types of human cancer as well as inflammatory, autoimmune, vascular and kidney diseases [1].
• Axl is a receptor tyrosine kinase originally identified as a transforming gene product in human myeloid leukemia cells [2].
• Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis [3].

High impact information on Axl

• BACKGROUND & AIMS: The growth arrest-specific gene 6 (Gas6) protein is a vitamin K-dependent protein that binds to the Axl subfamily of tyrosine kinase receptors and exerts antiapoptotic and proliferative effects [4].
• Cultured rat vascular smooth muscle cells also express Axl, where it has been proposed that Axl may play a role in cell proliferation [2].
• Other studies, performed in cultured rat vascular smooth muscle cells, revealed positive regulation of Axl mRNA expression by thrombin or angiotensin II but not by basic fibroblast growth factor, platelet-derived growth factor-BB, or transforming growth factor-ss1 [2].
• Northern blot analysis indicated increased mRNA expression for the secreted Axl ligand, Gas6, in injured carotids, with a time course paralleling that of Axl upregulation [2].
• The related Axl, Sky and Mer receptor tyrosine kinases (RTKs) are increasingly being implicated in a host of discrete cellular responses including cell survival, proliferation, migration and phagocytosis [1].

Biological context of Axl

• These Axl overexpressors exhibited 2-5-fold increased sensitivity to GAS6-induced chemotaxis [5].
• Inhibition of Gas6 by warfarin and the extracellular domain of its receptor, Axl, abolished phosphorylation of STAT3 in vivo [6].
• Therefore, we examined the gene expression of Gas6 and its receptors Rse, Axl, and Mer in a rat model of CR [7].
• In the present study we tested the mechanisms by which Axl regulates vascular smooth muscle cell (VSMC) growth focusing on its ability to inhibit apoptosis [8].
• Tyro-3, Axl, and Mer are three related receptor protein-tyrosine kinases (RPTKs) characterized by an extracellular domain exhibiting significant amino acid sequence similarity to neural cell adhesion molecules [9].

Anatomical context of Axl

• WB-F344 cells, a hepatocytic precursor cell line, also expressed Gas6 and Axl [4].
• Our results implicate Axl as a potential mediator of vascular smooth muscle migration and proliferation caused by vascular injury and G protein-coupled receptor agonists [2].
• These findings indicate that the Gas6/Axl pathway plays a key role in mesangial cell proliferation in vivo, and could be a potentially important therapeutic target for the treatment of renal disease [3].
• Sky, but not Axl, immunoreactivity was observed in the adult hippocampus [10].
• Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system [9].

Associations of Axl with chemical compounds

• Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases [1].
• Western blot analysis confirmed these results, showing that Axl protein expression was specifically increased by thrombin or angiotensin II [2].

Other interactions of Axl

• CONCLUSIONS: Our data demonstrate an expression of Gas6 and of its receptor Axl by oval cells during hepatic regeneration [4].

Analytical, diagnostic and therapeutic context of Axl

• Axl mRNA hepatic levels paralleled the number of oval cells, and immunohistochemistry showed Axl expression in these cells [4].

References