Wnt pathway

The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.

The Wnt pathway involves a large number of proteins that can regulate the production of Wnt signaling molecules, their interactions with receptors on target cells and the physiological responses of target cells that result from the exposure of cells to the extracellular Wnt ligands. Although the presence and strength of any given effect depends on the Wnt ligand, cell type, and organism, some components of the signaling pathway are remarkably conserved in a wide variety of organisms, from Caenorhabditis elegans to humans. Protein homology suggests that several distinct Wnt ligands were present in the common ancestor of all bilaterian life, and certain aspects of Wnt signaling are present in sponges and even in slime molds.

cMET Pathway Animation

MET activation by its ligand HGF induces MET kinase catalytic activity, which triggers transphosphorylation of the tyrosines Tyr 1234 and Tyr 1235. These two tyrosines engage various signal transducers, thus initiating a whole spectrum of biological activities driven by MET, collectively known as the invasive growth program. The transducers interact with the intracellular multisubstrate docking site of MET either directly, such as GRB2, SHC,[12] SRC, and the p85 regulatory subunit of phosphatidylinositol-3 kinase (PI3K),[12] or indirectly through the scaffolding protein Gab1[13] Tyr 1349 and Tyr 1356 of the multisubstrate docking site are both involved in the interaction with GAB1, SRC, and SHC, while only Tyr 1356 is involved in the recruitment of GRB2, phospholipase C γ (PLC-γ), p85, and SHP2.[14] GAB1 is a key coordinator of the cellular responses to MET and binds the MET intracellular region with high avidity, but low affinity.[15] Upon interaction with MET, GAB1 becomes phosphorylated on several tyrosine residues which, in turn, recruit a number of signalling effectors, including PI3K, SHP2, and PLC-γ. GAB1 phosphorylation by MET results in a sustained signal that mediates most of the downstream signaling pathways.

VEGF and EGFR pathways Ani,ation

The vascular endothelial growth factor (VEGF) family is composed of several isotypes, including VEGF (VEGF-A, vascular permeability factor), VEGF-B, VEGF-C and VEGF-D which exist as numerous splice variant isoforms. VEGF is a heparin-binding, disulfide-linked dimer glycoprotein that exists in various secreted isoforms, VEGF121, VEGF145 and VEGF165 and a membrane bound VEGF189. It shares significant homology with PDGF-A and PDGF-B. VEGF-B splice variants include a soluble VEGF-B167 form and a cell surface associated VEGF-B186 form. VEGF is able to heterodimerize with other forms of VEGF. It can form a heterodimer with VEGF-B, or non-VEGF factors such as placenta growth factor (PlGF). The existence of multiple VEGF isotypes and isoforms and their ability to heterodimerize provides for sophisticated tissue-specific regulation of cellular processes.

Members of the VEGF family promote two very important processes in vivo, angiogenesis and lymphangiogenesis, which involve growth of new blood and lymphatic vessels from pre-existing vasculature, respectively. These processes control the normal processes of wound healing, ovarian-follicular development, endometrium growth and pathological processes such as retinopathies, rheumatoid arthritis and solid tumor growth. Lymphangiogenesis is correlated with lymph node metastasis and cancer spread via the lymphatic system.