Essential role of PDK1 in regulating endothelial cell migration

Luca Primo, Laura Di Blasio, Cristina Roca, Sara Droetto, Roberto Piva, Brian Schaffhausen, Federico Bussolino

Research output: Contribution to journalArticlepeer-review

Abstract

The serine/threonine protein kinase phosphoinositide-dependent kinase 1 (PDK1) plays a central role in cellular signaling by phosphorylating members of the AGC family of kinases, including PKB/Akt. We now present evidence showing that PDK1 is essential for the motility of vascular endothelial cells (ECs) and that it is involved in the regulation of their chemotaxis. ECs differentiated from mouse embryonic stem cells lacking PDK1 completely lost their ability to migrate in vitro in response to vascular endothelial growth factor-A (VEGF-A). In addition, PDK1?/? embryoid bodies exhibit evident developmental and vascular defects that can be attributed to a reduced cell migration. Moreover, the overexpression of PDK1 increased the EC migration induced by VEGF-A. We propose a model of spatial distribution of PDK1 and Akt in which the synthesis of phosphatidylinositol 3,4,5 triphosphate at plasma membrane by activation of phosphoinositide 3-kinase recruits both proteins at the leading edge of the polarized ECs and promotes cell chemotaxis. These findings establish a mechanism for the spatial localization of PDK1 and its substrate Akt to regulate directional migration.

Original languageEnglish
Pages (from-to)1035-1047
Number of pages13
JournalJournal of Cell Biology
Volume176
Issue number7
DOIs
Publication statusPublished - Mar 26 2007

ASJC Scopus subject areas

  • Cell Biology

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