Click For Photo: https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/hires/2019/scientistssu.jpg
Growth factors are ligands that play important roles in the body—they are responsible for tissue regeneration, wound healing, and the maintenance and growth of cells. Stimulating growth factor-dependent pathways is therefore an important therapeutic strategy to promote the regeneration of tissues due to injuries and diseases. Using synthetic substitutes of growth factors is the primary method for artificially stimulating the desired pathways. However, synthetic substitutes are often not as efficient and comprehensive in inducing the required biological changes. Kunio Matsumoto at Kanazawa University and colleagues have recently created a substitute for one such growth factor, that produces a comparable biological response.
The hepatocyte growth factor (HGF) binds to and activates a receptor known as MET (Fig. 1). In other words, HGF is a native ligand for the MET receptor. The MET receptor is a transmembrane protein. Upon extracellular binding of HGF to the extracellular region of MET, pairing of the receptors (called 'dimerization') occurs, which allows the intracellular chemical change of the receptors (called 'phosphorylation'). This receptor phosphorylation means receptor activation, which triggers activation of intracellular biological signal transduction pathways, leading to a variety of biological responses in cells.
Actions - HGF - Researchers - Peptide - Molecule
To mimic the actions of HGF, the researchers created a macrocyclic peptide molecule (aMD5-PEG11) that activates the MET receptor (main fig). This molecule is composed of two chemically cross-linked macrocyclic peptides. Such cyclic molecules are flexible in structure and can bind and activate MET. Furthermore, aMD5-PEG11 docks at a different region of MET than HGF; aMD-PEG11 and HGF therefore did not directly compete for MET and nullify each other's effects. Whether aMD-PEG11 also induced these structural changes was then assessed in two different human cell types. aMD-PEG11 induced the same extent of coupling/dimerization and phosphorylation of the MET receptor in a comparable ability to HGF.
If the structural changes induced by HGF...
Wake Up To Breaking News!