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This study assessed the consequences of the downregulation or deletion of AKAP12 on endothelial cell migration and angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The consequences of siRNA\u2010mediated downregulation AKAP12 were studied in primary cultures of human endothelial cells as well as in endothelial cells and retinas from wild\u2010type versus AKAP12<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Molecular interactions were investigated using a combination of immunoprecipitation and mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AKAP12 was expressed at low levels in confluent endothelial cells but its expression was increased in actively migrating cells, where it localized to lamellipodia. In the postnatal retina, AKAP12 was expressed by actively migrating tip cells at the angiogenic front, and its deletion resulted in defective extension of the vascular plexus. In migrating endothelial cells, AKAP12 was co\u2010localized with the PKA type II\u2010\u03b1 regulatory subunit as well as multiple key regulators of actin dynamics and actin filament\u2010based movement; including components of the Arp2\/3 complex and the vasodilator\u2010stimulated phosphoprotein (VASP). Fitting with the evidence of a physical VASP\/AKAP12\/PKA complex, it was possible to demonstrate that the VEGF\u2010stimulated and PKA\u2010dependent phosphorylation of VASP was dependent on AKAP12. Indeed, AKAP12 colocalized with phospho\u2010Ser157 VASP at the leading edge of migrating endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results suggest that compartmentalized AKAP12\/PKA signalling mediates VASP phosphorylation at the leading edge of migrating endothelial cells to translate angiogenic stimuli into altered actin dynamics and cell movement.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13325","type":"journal-article","created":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T17:16:13Z","timestamp":1559668573000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["AKAP12 deficiency impairs VEGF\u2010induced endothelial cell migration and sprouting"],"prefix":"10.1111","volume":"228","author":[{"given":"Peter M.","family":"Benz","sequence":"first","affiliation":[{"name":"Institute for Vascular Signalling, Centre for Molecular Medicine Goethe University 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