Figure 1.

Plausible mode of functioning of cMET receptor (1) cMET is synthesized by hepatocytes. α subunit is extracellular; whereas the β subunit is trans-membrane peptide possessing a kinase domain and docking site for molecule which participate in cell signaling and receptor bioactivity (2) upon ligand binding to the cMET receptor, the tyrosine kinase domain is highly phosphorylated at tyrosine residue (1234–1235, 1349, 1356 at C terminus of β subunit) (3) Grb2 effecter binds to phosphorylated tyrosine kinase and RAS guanine exchange factor SOS (Son of sevenless) (4) SOS promotes dissociation of GDP from Ras and attachment of GTP thereby activates Ras (5) Ras activates Raf and in turn (6) Phosphorylates MEK, followed by phosphorylation of MAPK; LF cleaves MEKs and prevent further downstream signaling required for cell proliferation, survival and growth. (7) MAPK activates Myc (7A) and CREB (7B) by phosphorylation and (8) These translocates into nucleus and bind to their respective response elements (9) Gab1 interacts with cMet receptor and provide binding site for SH2 domain containing proteins (Grb2, PI3K, PLCγ) (10) PI3K phosphorylates Akt, which in turn (11) phosphorylates CREB and (12) allow transcription of surviving genes (also 7B) (13) Post phosphorylation C terminus of β subunit of the receptor acts as docking site for STAT3 and STAT3 is phosphorylated (14) Dimerized and translocated to nucleus for promoting different gene expressions.