Hepatocyte growth factor receptor

File:Met Gene.jpg

Met Gene

Hepatocyte Growth Factor Receptor (HGFR), also known as MET, is a protein encoded by the MET gene in humans. This receptor is a tyrosine kinase type, which plays a crucial role in cellular processes including growth, development, and regeneration. It is primarily recognized for its interaction with its ligand, Hepatocyte Growth Factor (HGF), which activates a wide range of cellular signaling pathways involved in cell proliferation, survival, motility, and morphogenesis.

Structure

The structure of the Hepatocyte Growth Factor Receptor consists of a single alpha chain and a beta chain that are produced from a single precursor polypeptide. The alpha chain and beta chain are linked by a disulfide bond. The extracellular region of the receptor binds to HGF, and the intracellular region has tyrosine kinase activity that is activated upon ligand binding.

Function

The primary function of HGFR is to mediate the effects of HGF, also known as scatter factor. This interaction is critical for embryonic development and wound healing in adults. Upon HGF binding, HGFR undergoes autophosphorylation, which activates its kinase activity. This activation triggers a cascade of downstream signaling pathways, including the RAS-MAPK pathway, PI3K-AKT pathway, and the STAT pathway, which are involved in cell proliferation, survival, and migration.

Clinical Significance

Alterations in the MET gene, including mutations, amplifications, or overexpression, have been implicated in the development and progression of various types of cancer. These alterations can lead to aberrant activation of HGFR signaling, promoting tumor growth, invasion, and metastasis. Consequently, HGFR is a target for cancer therapy, with several inhibitors developed to block its activity.

In addition to cancer, aberrant HGFR signaling has been associated with other diseases, such as pulmonary fibrosis and cardiovascular diseases, making it a potential therapeutic target beyond oncology.

Therapeutic Target

Given its role in cancer and other diseases, HGFR has been targeted for therapeutic intervention. Several strategies have been employed, including small molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies that block HGF binding to HGFR, and decoy receptors that sequester HGF. These therapies aim to inhibit the aberrant signaling pathways activated by HGFR, thereby suppressing tumor growth and metastasis.

Research Directions

Research continues to explore the full spectrum of HGFR's roles in health and disease, including its potential in regenerative medicine. Given its critical role in liver regeneration, there is interest in harnessing HGFR signaling for treating liver diseases. Additionally, understanding the mechanisms of resistance to HGFR-targeted therapies in cancer is a significant focus, aiming to develop more effective and durable treatments.

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