Phospholipase C gamma activation, phosphotidylinositol hydrolysis, and calcium mobilization are not required for FGF receptor-mediated chemotaxis.
Basic fibroblast growth factor (FGF) is a potent angiogenic factor that stimulates several cell types to migrate along a chemotactic gradient. Most chemoattractant receptors appear to share a common mechanism that involves activation of phospholipase C (PLC), hydrolysis of phosphotidylinositol, and mobilization of intracellular calcium. We transfected two different cell lines with either human FGF receptor-1 cDNA or chimeric FGF receptor cDNA. Ligand stimulation induced chemotaxis, activation of PLC gamma, phosphotidylinositol hydrolysis, and calcium mobilization in both wild-type receptor cell lines. No such response was elicited in control cells. Mutation of the two fibroblast growth factor receptors at residue 766, replacing tyrosine with phenylalanine, made the receptors incapable of associating with and activating PLC gamma following ligand stimulation. These mutant receptors also failed to mediate phosphotidylinositol hydrolysis and calcium mobilization. However, cells transfected with the mutant fibroblast growth factor receptors were as chemotactically responsive to the appropriate ligand as were cells transfected with the wild-type receptors. These findings demonstrate that the ability of the fibroblast growth factor receptor to promote chemotaxis is not dependent on increased activation of PLC gamma, increased hydrolysis of phosphotidylinositol, or increased global mobilization of calcium.
Clyman
R I
RI
Department of Pediatrics, University of California, San Francisco 94143.
Peters
K G
KG
Chen
Y Q
YQ
Escobedo
J
J
Williams
L T
LT
Ives
H E
HE
Wilson
E
E
D000818:Animals; D016466:CHO Cells / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002633:Chemotaxis / Q000502:physiology*; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D016297:Mutagenesis, Site-Directed; D010716:Phosphatidylinositols / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism*
D018076:DNA, Complementary; D010716:Phosphatidylinositols; D017468:Receptors, Fibroblast Growth Factor; D010738:Type C Phospholipases; D002118:Calcium