Signaling by MET

Activation of PLC gamma 1 (PLCG1) signaling by MET remains unclear. It has been reported that PLCG1 can bind to MET directly or be recruited by phosphorylated GAB1. Tyrosine residue Y307 of GAB1 that serves as docking sites for PLCG1 may be phosphorylated either by activated MET or SRC. Another PCLG1 docking site on GAB1, tyrosine residue Y373, was reported as the SRC target, while the kinase for the main PLCG1 docking site, Y407 of GAB1, is not known.

Signaling by MET promotes cell growth, cell survival and motility, which are essential for embryonic development and tissue regeneration. MET signaling is frequently aberrantly activated in cancer, through MET overexpression or activating MET mutations.

Considerable progress has recently been made in the development of HGF-MET inhibitors in cancer therapy. These include inhibitors of HGF activators, HGF inhibitors and MET antagonists, which are protein therapeutics that act outside the cell. Kinase inhibitors function inside the cell and have constituted the largest effort towards MET-based therapeutics.

Pathogenic bacteria of the species Listeria monocytogenes, exploit MET receptor as an entryway to host cells.

For review of MET signaling, please refer to Birchmeier et al. 2003, Trusolino et al. 2010, Gherardi et al. 2012, Petrini 2015.