Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l 3

Nisha Durand, Ligia I. Bastea, Jason Long, Heike Döppler, Kun Ling, Peter Storz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Focal adhesions (FAs) are highly dynamic structures that are assembled and disassembled on a continuous basis. The balance between the two processes mediates various aspects of cell behavior, ranging from cell adhesion and spreading to directed cell migration. The turnover of FAs is regulated at multiple levels and involves a variety of signaling molecules and adaptor proteins. In the present study, we show that in response to integrin engagement, a subcellular pool of Protein Kinase D1 (PKD1) localizes to the FAs. PKD1 affects FAs by decreasing turnover and promoting maturation, resulting in enhanced cell adhesion. The effects of PKD1 are mediated through direct phosphorylation of FA-localized phosphatidylinositol-4-phosphate 5-kinase type-l 3 (PIP5Kl 3) at serine residue 448. This phosphorylation occurs in response to Fibronectin-RhoA signaling and leads to a decrease in PIP5Kl 3s' lipid kinase activity and binding affinity for Talin. Our data reveal a novel function for PKD1 as a regulator of FA dynamics and by identifying PIP5Kl3 as a novel PKD1 substrate provide mechanistic insight into this process.

Original languageEnglish (US)
Article number35963
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 24 2016

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Focal Adhesions
Cell Adhesion
Protein Kinases
Phosphorylation
Talin
Focal Adhesion Protein-Tyrosine Kinases
Fibronectins
Integrins
Serine
Cell Movement
Phosphotransferases
1-phosphatidylinositol-4-phosphate 5-kinase
Lipids
Proteins

ASJC Scopus subject areas

  • General

Cite this

Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l 3. / Durand, Nisha; Bastea, Ligia I.; Long, Jason; Döppler, Heike; Ling, Kun; Storz, Peter.

In: Scientific Reports, Vol. 6, 35963, 24.10.2016.

Research output: Contribution to journalArticle

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AU - Storz, Peter

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