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 language | English |
|---|---|
| Pages (from-to) | 1035-1047 |
| Number of pages | 13 |
| Journal | Journal of Cell Biology |
| Volume | 176 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Mar 26 2007 |
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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 journal › Article
}
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.
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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 -