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 wildtype fibroblast growth factor recep tor-1 or a mutant receptor (Y766F) unable to bind phospholipase C-gamma, St imulation of cells expressing the wild-type receptor resulted in activation of phospholipases C, D and A(2) and increased phosphoinositide 3-kinase ac tivity. Stimulation of the wild-type receptor also resulted in stress fibre formation and a cellular shape change. Cells expressing the Y766F mutant r eceptor failed to stimulate phospholipase C, D and A(2) as well as phosphoi nositide 3-kinase, Furthermore, no stress fibre formation or shape change w as observed. Both the wild-type and Y766F receptor mutant activated MAP kin ase and elicited proliferative responses in the porcine aortic endothelial cells, Thus, fibroblast growth factor receptor-1 mediated activation of pho spholipases C, D and A(2) and phosphoinositide 3-kinase was dependent on ty rosine 766. Furthermore, whilst tyrosine 766 was not required for a prolife rative response, it was required for fibroblast growth factor receptor-1 me diated cytoskeletal.