scholarly journals Structural Basis for Phosphatidylinositol Phosphate Kinase Type Iγ Binding to Talin at Focal Adhesions

2004 ◽  
Vol 280 (9) ◽  
pp. 8381-8386 ◽  
Author(s):  
Jose M. de Pereda ◽  
Kate L. Wegener ◽  
Eugenio Santelli ◽  
Neil Bate ◽  
Mark H. Ginsberg ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Structural Basis ◽  
Phosphatidylinositol Phosphate ◽  
Phosphatidylinositol Phosphate Kinase

Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions

Nature ◽  
2002 ◽  
Vol 420 (6911) ◽  
pp. 89-93 ◽  
Author(s):  
Kun Ling ◽  
Renee L. Doughman ◽  
Ari J. Firestone ◽  
Matthew W. Bunce ◽  
Richard A. Anderson
Keyword(s):  
Focal Adhesions ◽  
Phosphatidylinositol Phosphate ◽  
Phosphatidylinositol Phosphate Kinase

scholarly journals Tyrosine phosphorylation of type Iγ phosphatidylinositol phosphate kinase by Src regulates an integrin–talin switch

2003 ◽  
Vol 163 (6) ◽  
pp. 1339-1349 ◽  
Author(s):  
Kun Ling ◽  
Renee L. Doughman ◽  
Vidhya V. Iyer ◽  
Ari J. Firestone ◽  
Shawn F. Bairstow ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Focal Adhesions ◽  
Fold Increase ◽  
Signaling Proteins ◽  
Integrin Receptors ◽  
Dynamic Regulation ◽  
Phosphatidylinositol Phosphate ◽  
Precise Role ◽  
Phosphatidylinositol Phosphate Kinase

Engagement of integrin receptors with the extracellular matrix induces the formation of focal adhesions (FAs). Dynamic regulation of FAs is necessary for cells to polarize and migrate. Key interactions between FA scaffolding and signaling proteins are dependent on tyrosine phosphorylation. However, the precise role of tyrosine phosphorylation in FA development and maturation is poorly defined. Here, we show that phosphorylation of type Iγ phosphatidylinositol phosphate kinase (PIPKIγ661) on tyrosine 644 (Y644) is critical for its interaction with talin, and consequently, localization to FAs. PIPKIγ661 is specifically phosphorylated on Y644 by Src. Phosphorylation is regulated by focal adhesion kinase, which enhances the association between PIPKIγ661 and Src. The phosphorylation of Y644 results in an ∼15-fold increase in binding affinity to the talin head domain and blocks β-integrin binding to talin. This defines a novel phosphotyrosine-binding site on the talin F3 domain and a “molecular switch” for talin binding between PIPKIγ661 and β-integrin that may regulate dynamic FA turnover.

scholarly journals Type I Phosphatidylinositol Phosphate Kinase Beta Regulates Focal Adhesion Disassembly by Promoting β1 Integrin Endocytosis

2010 ◽  
Vol 30 (18) ◽  
pp. 4463-4479 ◽  
Author(s):  
Wei-Ting Chao ◽  
Felicity Ashcroft ◽  
Alexes C. Daquinag ◽  
Tegy Vadakkan ◽  
Zhubo Wei ◽  
...  
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Type I ◽  
Adhesion Sites ◽  
Phosphatidylinositol Phosphate ◽  
Β1 Integrins ◽  
Focal Adhesion Turnover ◽  
Dynamin 2 ◽  
Phosphatidylinositol Phosphate Kinase

ABSTRACT Cell migration requires the regulated disassembly of focal adhesions, but the underlying mechanisms remain poorly defined. We have previously shown that focal adhesion disassembly requires the dynamin 2- and clathrin-dependent endocytosis of ligand-activated β1 integrins. Here, we identify type I phosphatidylinositol phosphate kinase beta (PIPKIβ), an enzyme that generates phosphatidylinositol-4,5-bisphosphate (PI4,5P2), as a key regulator of this process. We found that knockdown of PIPKIβ by RNA interference blocks the internalization of active β1 integrins and impairs focal adhesion turnover and cell migration. These defects are caused by the failure to target the endocytic machinery, including clathrin adaptors and dynamin 2, to focal adhesion sites. As a consequence, depletion of PIPKIβ blocks clathrin assembly at adhesion plaques and prevents complex formation between dynamin 2 and focal adhesion kinase (FAK), a critical step in focal adhesion turnover. Together, our findings identify PIPKIβ as a novel regulator of focal adhesion disassembly and suggest that PIPKIβ spatially regulates integrin endocytosis at adhesion sites to control cell migration.

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