Abstract
Endothelial cell spreading, migration, and morphogenesis are essential for angiogenesis, the formation of new blood vessels. In the present study, we explored roles of tyrosine kinase Pyk2 in angiogenesis of pulmonary endothelial cells. We found that tyrosine kinase Pyk2 was particularly enriched in pulmonary vascular endothelial cells and lung, a major organ site for tumor metastasis. By using adenovirus-mediated expression of various Pyk2 mutants, we demonstrated that Pyk2 tyrosine kinase activity was essential for the pulmonary vascular endothelial cell spreading, migration, morphogenesis, as well as pulmonary vein and artery angiogenesis ex vivo. We further showed that Pyk2 kinase activity was required for the expression of focal adhesion kinase, p130Crk-associated substrate, and its homologue human enhancer of filamentation 1, thus regulating formation of focal adhesions and cytoskeletal reorganization. These results indicate that Pyk2 plays a crucial role in the pulmonary endothelial cell motility such as spreading and migration necessary for angiogenesis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing
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Adenoviridae / genetics
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Animals
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CHO Cells
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Cell Adhesion
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Cell Line
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Cell Movement
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Cells, Cultured
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Cricetinae
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Endothelium / cytology
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Endothelium / metabolism
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Endothelium, Vascular / cytology*
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Focal Adhesion Kinase 1
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Focal Adhesion Kinase 2
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Focal Adhesion Protein-Tyrosine Kinases
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Humans
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Immunoblotting
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Lung / cytology*
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Mice
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Microscopy, Fluorescence
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Mutation
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Neoplasm Metastasis
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Neovascularization, Physiologic*
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Phosphoproteins / biosynthesis
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Phosphorylation
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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / chemistry*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-crk
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Tumor Cells, Cultured
Substances
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Adaptor Proteins, Signal Transducing
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Crk protein, rat
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NEDD9 protein, human
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Phosphoproteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Kinase 2
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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Ptk2 protein, mouse
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Ptk2 protein, rat
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Ptk2b protein, mouse
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Ptk2b protein, rat