Abstract
Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase-related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration.
| Original language | English |
|---|---|
| Pages (from-to) | 415-434 |
| Number of pages | 20 |
| Journal | Journal of Cell Biology |
| Volume | 206 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Cell Biology
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PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction. / Gagliardi, Paolo Armando; di Blasio, Laura; Puliafito, Alberto; Seano, Giorgio; Sessa, Roberto; Chianale, Federica; Leung, Thomas; Bussolino, Federico; Primo, Luca.
In: Journal of Cell Biology, Vol. 206, No. 3, 2014, p. 415-434.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction
AU - Gagliardi, Paolo Armando
AU - di Blasio, Laura
AU - Puliafito, Alberto
AU - Seano, Giorgio
AU - Sessa, Roberto
AU - Chianale, Federica
AU - Leung, Thomas
AU - Bussolino, Federico
AU - Primo, Luca
PY - 2014
Y1 - 2014
N2 - Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase-related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration.
AB - Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase-related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration.
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UR - http://www.scopus.com/inward/citedby.url?scp=84905973996&partnerID=8YFLogxK
U2 - 10.1083/jcb.201312090
DO - 10.1083/jcb.201312090
M3 - Article
C2 - 25092657
AN - SCOPUS:84905973996
VL - 206
SP - 415
EP - 434
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 3
ER -