Type Iγ phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration

Yue Sun, Kun Ling, Matthew P. Wagoner, Richard A. Anderson

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 Iγ phosphatidylinositol phosphate kinase 661 (PIPKIγ661), 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, PIPKIγ661 modulates nascent adhesion formation at the leading edge to facilitate cell migration. The epidermal growth factor (EGF) receptor directly phosphorylates PIPKIγ661 at tyrosine 634, and this event is required for EGF-induced migration. This phosphorylation regulates the interaction between PIPKIγ661 and phospholipase Cγ1 (PLCγ1, an enzyme previously shown to be involved in the regulation of EGF-stimulated migration). Our results suggest that phosphorylation events regulating specific PIPKIγ661 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.

Original languageEnglish (US)
Pages (from-to)297-308
Number of pages12
JournalJournal of Cell Biology
Volume178
Issue number2
DOIs
StatePublished - Jul 16 2007
Externally publishedYes

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Phosphatidylinositol Phosphates
Epidermal Growth Factor
Cell Movement
Phosphotransferases
Intercellular Signaling Peptides and Proteins
Phosphorylation
Talin
Enzymes
G-Protein-Coupled Receptors
Phosphatidylinositols
Epidermal Growth Factor Receptor
Tyrosine
Actins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Type Iγ phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. / Sun, Yue; Ling, Kun; Wagoner, Matthew P.; Anderson, Richard A.

In: Journal of Cell Biology, Vol. 178, No. 2, 16.07.2007, p. 297-308.

Research output: Contribution to journalArticle

Sun, Yue ; Ling, Kun ; Wagoner, Matthew P. ; Anderson, Richard A. / Type Iγ phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. In: Journal of Cell Biology. 2007 ; Vol. 178, No. 2. pp. 297-308.
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