Figure 1712

Model of hepatocyte growth factor (HGF)/c-met signal transduction. In the extracellular space, single-chain precursors of HGF bound to the proteoglycans at the cell surface are converted to the active form by urokinase plasminogen activator (uPA), while the matrix soluble precursor is processed by a serum derived pro-HGF convertase. HGF, upon binding to its receptor c-met, induces its dimerization as well as autophosphorylation of tyrosine residues. The phosphorylated residue binds to various adaptors and signal transducers such as growth factor receptor bound pro-tein-2 (Grb2), p85-PI3 kinase, phospholi-pase C-gamma (PLC-gamma), signal transducer and activator of transcription-3 (STAT-3) and Src homology/collagen (SHC) via Src homology 2 (SH2) domains and triggers various signal transduction pathways. A common theme among tyrosine kinase receptors is that phosphorylation of different specific tyrosine residues determines which intracellular transducer will bind the receptor and be activated. In the case of HGF receptor, phosphorylation of a single multifunctional site triggers a pleiotropic response involving multiple signal transducers. The synchronous activation of several signaling pathways is essential to conferring the distinct invasive growth ability of the HGF receptor. HGF functions as a scattering (dissociation/motility) factor for epithelial cells, and this ability seems to be mediated through the activation of STAT-3.

Phosphorylation of adhesion complex regulatory proteins such as ZO-1, beta-catenin, and focal adhesion kinase (FAK) may occur via activation of c-src. Another Bcl2 interacting protein termed BAG-1 mediates the antiapoptotic signal of HGF receptor by a mechanism of receptor association independent from tyrosine residues.




Alter leukocyte function

Cell migration

Alter inflammatory process





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