The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.
VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments.
School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
Gina A
GA
Smith
School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
Gareth W
GW
Fearnley
School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
Darren C
DC
Tomlinson
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, U.K.
Michael A
MA
Harrison
School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K. s.ponnambalam@leeds.ac.uk.
Sreenivasan
S
Ponnambalam
D000818:Animals; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D021381:Protein Transport; D059748:Proteolysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000737:chemistry / Q000378:metabolism*
D042442:Vascular Endothelial Growth Factors; D040262:Receptors, Vascular Endothelial Growth Factor
disease; drugs; isoforms; membrane trafficking; receptor tyrosine kinase; signal transduction; vascular endothelial growth factor (VEGF)