Protein kinase D1 regulates VEGF-A-induced αvβ3 integrin trafficking and endothelial cell migration

Laura di Blasio, Sara Droetto, Jim Norman, Federico Bussolino, Luca Primo

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The bidirectional communication between integrin αvβ3 and vascular endothelial growth factor (VEGF) receptors acts to integrate and coordinate endothelial cell (EC) activity during angiogenesis. However, the molecular mechanisms involved in this signaling crosstalk are only partially revealed. We have found that protein kinase D1 (PKD1) was activated by VEGF-A, but not by other angiogenic factors, and associated with αvβ3 integrin. Moreover, knockdown of PKD1 increased endocytosis of αvβ3 and reduced its return from endosomes to the plasma membrane leading to accumulation of the integrin in Rab5- and Rab4-positive endosomes. Consistent with this, PKD1 knockdown caused defects in focal complex formation and reduced EC migration in response to VEGF-A. Moreover, knockdown of PKD1 reduced EC motility on vitronectin, whereas migration on collagen I was not PKD1 dependent. These results suggest that PKD1-regulated αvβ3 trafficking contributes to the angiogenesis process by integrating VEGF-A signaling with extracellular matrix interactions.

Original languageEnglish
Pages (from-to)1107-1118
Number of pages12
JournalTraffic
Volume11
Issue number8
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Endothelial cells
Integrins
Protein Kinases
Vascular Endothelial Growth Factor A
Cell Movement
Endothelial Cells
Endosomes
Vitronectin
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inducing Agents
Cell membranes
Crosstalk
Endocytosis
Extracellular Matrix
Collagen
Cell Membrane
Defects
Communication

Keywords

  • Angiogenesis
  • Cell migration
  • Endocytosis
  • Integrins
  • Recycling

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Protein kinase D1 regulates VEGF-A-induced αvβ3 integrin trafficking and endothelial cell migration. / di Blasio, Laura; Droetto, Sara; Norman, Jim; Bussolino, Federico; Primo, Luca.

In: Traffic, Vol. 11, No. 8, 08.2010, p. 1107-1118.

Research output: Contribution to journalArticle

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