Tyrosine phosphorylation of focal adhesion kinase stimulated by hepatocyte growth factor leads to mitogen-activated protein kinase activation.
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase involved in integrin-mediated signal transduction pathway. In this report, we describe that the treatment of hepatocyte growth factor (HGF) stimulates a significant increase in the tyrosine phosphorylation of FAK in human embryonic kidney 293 cells. This stimulation is independent of cell adhesion or the integrity of the actin cytoskeleton, suggesting potentially different mechanisms by which the HGF receptors and integrins regulate the tyrosine phosphorylation of FAK. Our results also suggest that the activation of Src upon HGF stimulation is likely to be one, if not the only, of the mechanisms responsible for the HGF-induced tyrosine phosphorylation of FAK. Furthermore, we showed that a mutation in the Grb2 binding site Tyr-925 of FAK partially abolishes its increase in HGF-induced phosphorylation. Finally, we demonstrated that HGF stimulates the association of FAK with Grb2 in vitro and in intact cells and provided evidence that FAK might contribute to the activation of mitogen-activated protein kinase through Ras in HGF signaling by functioning as an adapter molecule.
Chen
H C
HC
Department of Zoology, College of Agriculture, National Chung Hsing University, Taichung, Taiwan, Republic of China. hcchen@nchu.edu.tw
Chan
P C
PC
Tang
M J
MJ
Cheng
C H
CH
Chang
T J
TJ
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051380:GRB2 Adaptor Protein; D011905:Genes, ras / Q000235:genetics; D006388:Hemagglutinins / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D000939:Epitopes; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D006388:Hemagglutinins; D011506:Proteins; D019000:Phosphotyrosine; D015638:Cytochalasin D; D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases