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Published online
doi:10.1083/jcb.200701078
The Journal of Cell Biology, Vol. 178, No. 2, 297-308
The Rockefeller University Press, 0021-9525 $30.00
© Sun et al.
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Article

Type I{gamma} phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration



Yue Sun1, Kun Ling1, Matthew P. Wagoner2, and Richard A. Anderson2

1 Department of Pharmacology, School of Medicine and Public Health, and 2 Program in Molecular and Cellular Pharmacology, University of Wisconsin–Madison, Madison, WI 53706

Correspondence to Richard A. Anderson: raanders{at}wisc.edu

Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) modulates a plethora of cytoskeletal interactions that control the dynamics of actin assembly and, ultimately, cell migration. We show that the type I{gamma} phosphatidylinositol phosphate kinase 661 (PIPKI{gamma}661), an enzyme that generates PI4,5P2, is required for growth factor but not G protein–coupled receptor–stimulated directional migration. By generating PI4,5P2 and regulating talin assembly, PIPKI{gamma}661 modulates nascent adhesion formation at the leading edge to facilitate cell migration. The epidermal growth factor (EGF) receptor directly phosphorylates PIPKI{gamma}661 at tyrosine 634, and this event is required for EGF-induced migration. This phosphorylation regulates the interaction between PIPKI{gamma}661 and phospholipase C{gamma}1 (PLC{gamma}1, an enzyme previously shown to be involved in the regulation of EGF-stimulated migration). Our results suggest that phosphorylation events regulating specific PIPKI{gamma}661 interactions are required for growth factor–induced migration. These interactions in turn define the spatial and temporal generation of PI4,5P2 and derived messengers required for directional migration.

Abbreviations used in this paper: AP, adaptor protein; EGFR, EGF receptor; HGF, hepatocyte growth factor; LPA, lysophosphatidic acid; PI4,5P2, phosphatidylinositol 4,5-bisphosphate; PIPKI, type I phosphatidylinositol phosphate kinase; SDF, stromal cell–derived factor; shRNA, short hairpin RNA.


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