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 journalArticle

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

Fingerprint

1-Phosphatidylinositol 4-Kinase
Cell Movement
Endothelial Cells
Chemotaxis
Vascular Endothelial Growth Factor A
Embryoid Bodies
Aptitude
Protein-Serine-Threonine Kinases
Blood Vessels
Phosphotransferases
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology

Cite this

Essential role of PDK1 in regulating endothelial cell migration. / Primo, Luca; Di Blasio, Laura; Roca, Cristina; Droetto, Sara; Piva, Roberto; Schaffhausen, Brian; Bussolino, Federico.

In: Journal of Cell Biology, Vol. 176, No. 7, 26.03.2007, p. 1035-1047.

Research output: Contribution to journalArticle

Primo, Luca ; Di Blasio, Laura ; Roca, Cristina ; Droetto, Sara ; Piva, Roberto ; Schaffhausen, Brian ; Bussolino, Federico. / Essential role of PDK1 in regulating endothelial cell migration. In: Journal of Cell Biology. 2007 ; Vol. 176, No. 7. pp. 1035-1047.
@article{a75779c519e34e64bf4bbcd02ff58dbb,
title = "Essential role of PDK1 in regulating endothelial cell migration",
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.",
author = "Luca Primo and {Di Blasio}, Laura and Cristina Roca and Sara Droetto and Roberto Piva and Brian Schaffhausen and Federico Bussolino",
year = "2007",
month = "3",
day = "26",
doi = "10.1083/jcb.200607053",
language = "English",
volume = "176",
pages = "1035--1047",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - Essential role of PDK1 in regulating endothelial cell migration

AU - Primo, Luca

AU - Di Blasio, Laura

AU - Roca, Cristina

AU - Droetto, Sara

AU - Piva, Roberto

AU - Schaffhausen, Brian

AU - Bussolino, Federico

PY - 2007/3/26

Y1 - 2007/3/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33947728156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947728156&partnerID=8YFLogxK

U2 - 10.1083/jcb.200607053

DO - 10.1083/jcb.200607053

M3 - Article

C2 - 17371830

AN - SCOPUS:33947728156

VL - 176

SP - 1035

EP - 1047

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 7

ER -