The Role of Mitogen-Activated Protein Kinase Activation within Focal Adhesions in Chemotaxis toward FGF-2 by Murine Brain Capillary Endothelial Cells

Shono, Takefumi; Kanetake, Hiroshi; Kanda, Shigeru

doi:10.1006/excr.2001.5154

Cited by 62 publications

(47 citation statements)

References 53 publications

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“…Similar to cell proliferation, the chemotactic effect of FGF2 requires the activation of the MAPK signaling pathway [30] and is abolished by PKC down-regulation [31]. The capacity of FGFR1 to mediate chemotaxis resides in the amino acid stretch 759-773 of its cytoplasmic tail [32].…”

Section: Endothelial Cell Migrationmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,130

870

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Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. #

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Section: Endothelial Cell Migrationmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,130

870

View full text Add to dashboard Cite

show abstract

“…18,19 Signaling through these pathways promotes proliferation, survival and chemotaxis in endothelial cells and ultimately, produces the characteristic effects of VEGF on vessels, such as increased vascular permeability and angiogenesis. [20][21][22][23] These signaling pathways in endothelial cells can be activated not only by VEGF-VEGFR2 but also by other angiogenesis promoters (e.g., basic FGF) interacting with their cognate receptors and therefore, [24][25][26] may function as general indicators of angiogenic vessel activation.…”

Section: Introductionmentioning

confidence: 99%

Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors

Lassoued

Murphy

Tsai

et al. 2010

Cancer Biology & Therapy

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“…The assembly of focal adhesions in brain microvascular endothelial cells was reported (26,43). In this study, we explored the cell signaling proteins that couple VEGF binding to its receptors with focal adhesion assembly in HBMECs.…”

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confidence: 99%

Vascular Endothelial Growth Factor Regulates Focal Adhesion Assembly in Human Brain Microvascular Endothelial Cells through Activation of the Focal Adhesion Kinase and Related Adhesion Focal Tyrosine Kinase

Avraham

Lee

Koh

et al. 2003

Journal of Biological Chemistry

139

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Vascular endothelial growth factor (VEGF) plays a significant role in blood-brain barrier breakdown and angiogenesis after brain injury. VEGF-induced endothelial cell migration is a key step in the angiogenic response and is mediated by an accelerated rate of focal adhesion complex assembly and disassembly. In this study, we identified the signaling mechanisms by which VEGF regulates human brain microvascular endothelial cell (HBMEC) integrity and assembly of focal adhesions, complexes comprised of scaffolding and signaling proteins organized by adhesion to the extracellular matrix. We found that VEGF treatment of HBMECs plated on laminin or fibronectin stimulated cytoskeletal organization and increased focal adhesion sites. Pretreating cells with VEGF antibodies or with the specific inhibitor SU-1498, which inhibits Flk-1/KDR receptor phosphorylation, blocked the ability of VEGF to stimulate focal adhesion assembly. VEGF induced the coupling of focal adhesion kinase (FAK) to integrin ␣ v ␤ 5 and tyrosine phosphorylation of the cytoskeletal components paxillin and p130cas . Additionally, FAK and related adhesion focal tyrosine kinase (RAFTK)/Pyk2 kinases were tyrosine-phosphorylated by VEGF and found to be important for focal adhesion sites. Overexpression of wild type RAFTK/Pyk2 increased cell spreading and the migration of HBMECs, whereas overexpression of catalytically inactive mutant RAFTK/Pyk2 markedly suppressed HBMEC spreading (ϳ70%), adhesion (ϳ82%), and migration (ϳ65%). Furthermore, blocking of FAK by the dominant-interfering mutant FRNK (FAK-related non-kinase) significantly inhibited HBMEC spreading and migration and also disrupted focal adhesions. Thus, these studies define a mechanism for the regulatory role of VEGF in focal adhesion complex assembly in HBMECs via activation of FAK and RAFTK/Pyk2.

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The Role of Mitogen-Activated Protein Kinase Activation within Focal Adhesions in Chemotaxis toward FGF-2 by Murine Brain Capillary Endothelial Cells

Cited by 62 publications

References 53 publications

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors

Vascular Endothelial Growth Factor Regulates Focal Adhesion Assembly in Human Brain Microvascular Endothelial Cells through Activation of the Focal Adhesion Kinase and Related Adhesion Focal Tyrosine Kinase

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