Hepatocyte growth factor receptor

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Overview

The Hepatocyte Growth Factor Receptor (HGFR), also known as c-Met, is a protein that in humans is encoded by the MET gene. It is a receptor tyrosine kinase that is essential for embryonic development, organ regeneration, and wound healing. The receptor is activated by its ligand, Hepatocyte Growth Factor (HGF), which induces a variety of cellular responses including proliferation, motility, and morphogenesis.

Structure

The c-Met receptor is a single-pass transmembrane protein composed of an extracellular domain, a transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding to HGF and consists of a semaphorin domain, a plexin-semaphorin-integrin (PSI) domain, and four immunoglobulin-plexin-transcription (IPT) domains.

Function

Upon binding of HGF, c-Met undergoes dimerization and autophosphorylation on specific tyrosine residues within its intracellular domain. This phosphorylation creates docking sites for downstream signaling molecules, leading to the activation of several signaling pathways, including the PI3K/AKT pathway, RAS/MAPK pathway, and STAT pathway. These pathways are involved in regulating cell growth, survival, and differentiation.

Clinical Significance

Aberrant activation of c-Met has been implicated in various types of cancer, including lung cancer, breast cancer, and gastric cancer. Overexpression, gene amplification, and mutations of the MET gene can lead to constitutive activation of the receptor, promoting oncogenesis. As a result, c-Met is a target for cancer therapy, and several c-Met inhibitors are currently in clinical trials.

Therapeutic Targeting

Therapeutic strategies targeting c-Met include small molecule tyrosine kinase inhibitors, monoclonal antibodies against c-Met or HGF, and decoy receptors. These therapies aim to inhibit the aberrant signaling pathways activated by c-Met in cancer cells.

Research and Development

Ongoing research is focused on understanding the precise mechanisms of c-Met signaling and its role in cancer progression. Additionally, the development of biomarkers for predicting response to c-Met-targeted therapies is an active area of investigation.

Also see

• Hepatocyte Growth Factor
• Receptor Tyrosine Kinase
• Signal Transduction
• Cancer Therapy
• Oncogene