scholarly journals Tyrosine Phosphorylation of Growth Factor Receptor-bound Protein-7 by Focal Adhesion Kinase in the Regulation of Cell Migration, Proliferation, and Tumorigenesis

2009 ◽  
Vol 284 (30) ◽  
pp. 20215-20226 ◽  
Author(s):  
Pei-Yu Chu ◽  
Ling-Ya Huang ◽  
Chun-Hua Hsu ◽  
Chun-Chi Liang ◽  
Jun-Lin Guan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Growth Factor Receptor ◽  
Growth Factor Receptor Bound

Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells

2001 ◽  
Vol 360 (1) ◽  
pp. 255-264 ◽  
Author(s):  
Robin ABU-GHAZALEH ◽  
Jahangir KABIR ◽  
Haiyan JIA ◽  
Mel LOBO ◽  
Ian ZACHARY
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Growth Factor ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) stimulates the tyrosine phosphorylation of focal adhesion kinase (FAK), increases focal adhesion formation and is chemotactic for human umbilical-vein endothelial cells (HUVECs). In the present study we identified the major sites of VEGF-induced FAK tyrosine phosphorylation and investigated the mechanism mediating this pathway in the action of VEGF. VEGF increased the focal adhesion localization of FAK phosphorylated at Tyr-397 (Y397) and Y861 but stimulated a marked increase in phosphorylation at Y861 without significantly affecting the total level of phospho-Y397 FAK. Inhibition of Src with the specific inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) completely blocked VEGF-induced Y861 phosphorylation without decreasing the level of phospho-Y397 FAK. We also examined the role of Src in mediating endothelial functions of VEGF in which FAK has been implicated as having a role. PP2 markedly inhibited VEGF-induced chemotaxis and wound-healing cell migration. The Src inhibitor also decreased the anti-apoptotic effect of VEGF determined by surface staining of annexin V but did not increase FAK proteolysis or prevent the VEGF-dependent inhibition of FAK proteolysis. In contrast, the specific PtdIns 3-kinase inhibitor LY294002 induced apoptosis and markedly decreased p125FAK expression and increased FAK proteolysis but had little effect on Y861 phosphorylation. These findings identify Src-dependent FAK phosphorylation at Y861 as a novel VEGF-induced signalling pathway in endothelial cells and suggest that this pathway might be involved in the mechanisms mediating VEGF-induced endothelial cell migration and anti-apoptosis.

scholarly journals Spatial activation of ezrin by epidermal growth factor receptor and focal adhesion kinase co-ordinates epithelial cell migration

Open Biology ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 210166
Author(s):  
Grace K. Chan ◽  
John A. McGrath ◽  
Maddy Parsons
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Epidermal Growth ◽  
And Migration

Epidermal growth factor receptor (EGFR) plays a critical role in the promotion of epithelial cell proliferation and migration. Previous studies have suggested a cooperative role between EGFR and integrin signalling pathways that enable efficient adhesion and migration but the mechanisms controlling this remain poorly defined. Here, we show that EGFR forms a complex with focal adhesion kinase in epithelial cells. Surprisingly, this complex enhances local Src activity at focal adhesions to promote phosphorylation of the cytoskeletal adaptor protein ezrin at Y478, leading to actomyosin contractility, suppression of focal adhesion dynamics and slower migration. We further demonstrate this regulation of Src is due to the suppression of PTP1B activity. Our data provide new insight into EGF-independent cooperation between EGFR and integrins and suggest transient interactions between these kinases at the leading edge of cells act to spatially control signalling to permit efficient motility.

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