title: IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration.
abstract: Phosphatidylinositol 4,5 bisphosphate (PIP₂) is a key lipid messenger for regulation of cell migration. PIP₂ modulates many effectors, but the specificity of PIP₂ signalling can be defined by interactions of PIP₂-generating enzymes with PIP₂ effectors. Here, we show that type Iγ phosphatidylinositol 4-phosphate 5-kinase (PIPKIγ) interacts with the cytoskeleton regulator, IQGAP1, and modulates IQGAP1 function in migration. We reveal that PIPKIγ is required for IQGAP1 recruitment to the leading edge membrane in response to integrin or growth factor receptor activation. Moreover, IQGAP1 is a PIP₂ effector that directly binds PIP₂ through a polybasic motif and PIP₂ binding activates IQGAP1, facilitating actin polymerization. IQGAP1 mutants that lack PIPKIγ or PIP₂ binding lose the ability to control directional cell migration. Collectively, these data reveal a synergy between PIPKIγ and IQGAP1 in the control of cell migration.
authors: Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors: Suyong
authors: S
authors: Choi
authors: Narendra
authors: N
authors: Thapa
authors: Andrew C
authors: AC
authors: Hedman
authors: Zhigang
authors: Z
authors: Li
authors: David B
authors: DB
authors: Sacks
authors: Richard A
authors: RA
authors: Anderson
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D020703:ras GTPase-Activating Proteins / Q000502:physiology*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D019269:Phosphatidylinositol 4,5-Diphosphate; D020703:ras GTPase-Activating Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase
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