Modulation of cell spreading and migration by pp125FAK phosphorylation.
We provide evidence for both matrix-dependent and pp60v-src tyrosine kinase-dependent modulation of cell migration via tyrosine phosphorylation of pp125FAK, a focal adhesion kinase, thought to be involved in integrin-mediated signaling. Enhanced pp125FAK tyrosine phosphorylation and cell spreading was associated with decreased migration. Cells plated on type I collagen were less spread and exhibited lower levels of pp125FAK tyrosine phosphorylation and faster migration rates compared with cells on fibronectin that were well spread, which exhibited enhanced levels of pp125FAK tyrosine phosphorylation and slower migration rates. Inside-out signaling via expression of pp60v-src or its kinase-negative mutant caused a decrease in cell migration by changing the extent of pp125FAK tyrosine phosphorylation to above or below the levels obtained with control cells plated on fibronectin. Hence, pp125FAK tyrosine phosphorylation appears to play a role in the signaling cascade pathway involved in regulation of extracellular matrix-modulated, integrin-mediated cell migration.
Sankar
S
S
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Mahooti-Brooks
N
N
Hu
G
G
Madri
J A
JA
D016475:3T3 Cells; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002461:Cell Line, Transformed; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D009154:Mutation; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D015815:Cell Adhesion Molecules; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); C496051:Ptk2 protein, mouse