Autotaxin
Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is an enzyme that plays a crucial role in the lysophospholipid signaling pathway. It is encoded by the ENPP2 gene in humans. Autotaxin is a secreted glycoprotein that exhibits lysophospholipase D activity, which is responsible for the production of lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC).
Function
Autotaxin is involved in various biological processes, including cell proliferation, cell migration, and angiogenesis. It is a key enzyme in the LPA signaling pathway, which influences numerous physiological and pathological processes. LPA acts through its G protein-coupled receptors (GPCRs) to mediate its effects on cells.
Structure
Autotaxin is composed of several domains, including two somatomedin B-like domains, a central catalytic domain, and a C-terminal nuclease-like domain. The catalytic domain is responsible for its lysophospholipase D activity, which hydrolyzes LPC to produce LPA.
Clinical Significance
Autotaxin has been implicated in various diseases, including cancer, fibrosis, and inflammatory diseases. Elevated levels of autotaxin and LPA have been observed in several types of cancer, where they contribute to tumor growth, metastasis, and resistance to therapy. Inhibitors of autotaxin are being explored as potential therapeutic agents for these conditions.
Related Enzymes
Autotaxin belongs to the ectonucleotide pyrophosphatase/phosphodiesterase family (ENPP), which includes other enzymes such as ENPP1, ENPP3, and ENPP4. These enzymes share structural similarities and are involved in the hydrolysis of various nucleotide substrates.
Research
Ongoing research is focused on understanding the detailed mechanisms of autotaxin function, its role in disease, and the development of specific inhibitors. Studies are also exploring the potential of autotaxin as a biomarker for disease diagnosis and prognosis.
See Also
- Lysophosphatidic acid
- Lysophospholipase D
- Ectonucleotide pyrophosphatase/phosphodiesterase family
- G protein-coupled receptors
- Cell signaling
References
External Links
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Contributors: Prab R. Tumpati, MD