AXL receptor tyrosine kinase

AXL receptor tyrosine kinase (AXL) is a protein encoded by the AXL gene in humans. It is a member of the Tyrosine kinase family and the TAM subfamily, which also includes MER and TYRO3. AXL plays a critical role in various cellular processes, including growth, survival, differentiation, and migration. Its activity is implicated in the regulation of the immune response, cancer progression, and viral infection.

Function

AXL receptor tyrosine kinase is a receptor for the Vitamin K-dependent protein growth-arrest-specific gene 6 (Gas6). Binding of Gas6 to AXL triggers activation of its kinase domain, leading to autophosphorylation and subsequent phosphorylation of downstream targets. This activation initiates multiple signaling pathways, including the PI3K/AKT and the MAPK pathways, which are essential for cell survival and proliferation. AXL signaling is involved in the regulation of the immune system, promoting the survival of certain cell types under stress conditions, and facilitating the clearance of apoptotic cells.

Role in Disease

The aberrant expression or activation of AXL has been linked to a wide range of diseases, particularly cancer. In cancer cells, AXL can promote tumor growth, metastasis, and resistance to chemotherapy and targeted therapy. Its expression is often associated with a poor prognosis in various cancers, including breast, lung, and pancreatic cancers. AXL is also involved in the resistance mechanism against Tyrosine kinase inhibitors (TKIs), making it a target for cancer therapy.

In addition to cancer, AXL has been implicated in other pathological conditions such as viral infections, where it acts as an entry factor for certain viruses, and in chronic inflammatory diseases by regulating the immune response.

Therapeutic Target

Given its role in disease progression, especially in cancer and viral infections, AXL is considered a promising therapeutic target. Several strategies are being explored to inhibit AXL activity, including small molecule inhibitors, monoclonal antibodies, and decoy receptors. These therapeutic agents aim to block the interaction between AXL and Gas6, inhibit AXL's kinase activity, or downregulate its expression, thereby suppressing the downstream signaling pathways that contribute to disease progression.

Research

Research on AXL receptor tyrosine kinase is ongoing, with studies aimed at understanding its structure, signaling mechanisms, and role in disease. Efforts are also focused on developing and testing AXL inhibitors in preclinical and clinical settings to evaluate their efficacy and safety as potential treatments for cancer and other diseases.