Tyrosine 766 in the fibroblast growth factor receptor-1 is required for FGF-stimulation of phospholipase C, phospholipase D, phospholipase A(2), phosphoinositide 3-kinase and cytoskeletal reorganisation in porcine aortic endothelial cells.
Fibroblast growth factor-mediated signalling was studied in porcine aortic endothelial cells expressing either wild-type fibroblast growth factor receptor-1 or a mutant receptor (Y766F) unable to bind phospholipase C-(&ggr;). Stimulation of cells expressing the wild-type receptor resulted in activation of phospholipases C, D and A(2) and increased phosphoinositide 3-kinase activity. Stimulation of the wild-type receptor also resulted in stress fibre formation and a cellular shape change. Cells expressing the Y766F mutant receptor failed to stimulate phospholipase C, D and A(2) as well as phosphoinositide 3-kinase. Furthermore, no stress fibre formation or shape change was observed. Both the wild-type and Y766F receptor mutant activated MAP kinase and elicited proliferative responses in the porcine aortic endothelial cells. Thus, fibroblast growth factor receptor-1 mediated activation of phospholipases C, D and A(2) and phosphoinositide 3-kinase was dependent on tyrosine 766. Furthermore, whilst tyrosine 766 was not required for a proliferative response, it was required for fibroblast growth factor receptor-1 mediated cytoskeletal reorganisation.
Cross
M J
MJ
Department of Genetics, Rudbeck Laboratory, S-75185 Uppsala, Sweden. michael.cross@genpat.uu.se
Hodgkin
M N
MN
Roberts
S
S
Landgren
E
E
Wakelam
M J
MJ
Claesson-Welsh
L
L
D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics
D017468:Receptors, Fibroblast Growth Factor; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020928:Mitogen-Activated Protein Kinases; D010740:Phospholipases; D010741:Phospholipases A; D010738:Type C Phospholipases; D010739:Phospholipase D