Recombinant c-MET (N1049-G1346), receptor tyrosine kinase domain, cellular-mesenchymal epithelial transition factor

Our c-MET construct spans residues N1049-G1346 and comprises the receptor tyrosine kinase domain, including the two activation-loop phosphorylation sites Tyr1234 and Tyr1235. In addition, the construct contains the ATP-binding pocket, the catalytic loop and the C-terminal regulatory tail.

Protein Construct: c-MET(N1049-G1346)
Source: Human
Expression Host: Escherichia coli
Molecular weight [kDa]: 33.7
pI: 8.45
Extinction Coefficient [M^-1cm^-1]: 36900
Concentration: 10.1 mg/mL
Storage Buffer: 20 mM Tris-HCl pH 8.3, 100 mM NaCl, 10 % glycerol, 1 mM TCEP
Tag: none

Amino acid sequence:

QC Data: Datasheet
Purity SDS: >95 %
Hydrodynamic Radius (nm): 3.46
Polydispersity Index (PDI): 0.18
T_m (°C): 49.3
T_on (°C): 42.2

Structure and function

The receptor tyrosine kinase c-MET is a key component of the HGF/c-MET signaling pathway and plays important roles in embryogenesis, wound healing, tissue regeneration, and cell proliferation. c-MET is primarily expressed on epithelial cells and is activated by binding of its endogenous ligand, hepatocyte growth factor (HGF). HGF-induced receptor dimerization promotes c-MET autophosphorylation and activation of its intracellular tyrosine kinase domain, which catalyzes the transfer of phosphate groups from ATP to specific tyrosine residues. These phosphorylation events create docking sites for downstream signaling proteins and initiate signaling pathways that regulate cellular processes such as proliferation and survival.

The tyrosine kinase domain of c-MET as an important drug target

Under physiological conditions, c-MET activity is tightly controlled by negative feedback mechanisms that prevent excessive signaling. Following activation, c-MET can undergo ubiquitination and be internalized through endocytosis, followed by transport to lysosomes for degradation. In malignant tumor cells, these regulatory mechanisms can become disrupted, resulting in constitutive activation of c-MET that contributes to tumor growth and cancer progression.

Therapeutic strategies targeting c-MET include small-molecule tyrosine kinase inhibitors, monoclonal antibodies, and proteolysis-targeting chimeras (PROTACs). Small-molecule c-MET inhibitors can be classified according to their binding mode within the tyrosine kinase domain. Type I inhibitors bind to the ATP-binding site in the active kinase conformation, whereas Type II inhibitors engage the ATP-binding site and an adjacent allosteric pocket, stabilizing an inactive kinase conformation.