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Publication : The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha.

First Author  Kisseleva M Year  2005
Journal  Mol Cell Biol Volume  25
Issue  10 Pages  3956-66
PubMed ID  15870270 Mgi Jnum  J:99138
Mgi Id  MGI:3581335 Doi  10.1128/MCB.25.10.3956-3966.2005
Citation  Kisseleva M, et al. (2005) The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha. Mol Cell Biol 25(10):3956-66
abstractText  The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many actin-binding proteins and as such is an important modulator of cytoskeleton organization during cell migration, for example. In migrating cells actin remodeling is tightly regulated and localized; therefore, how the PI(4,5)P2 level is spatially and temporally regulated is crucial to understanding how it controls cell migration. Here we show that the LIM protein Ajuba contributes to the cellular regulation of PI(4,5)P2 levels by interacting with and activating the enzymatic activity of the PI(4)P 5-kinase (PIPKIalpha), the predominant enzyme in the synthesis of PI(4,5)P2, in a migration stimulus-regulated manner. In migrating primary mouse embryonic fibroblasts (MEFs) from Ajuba(-/-) mice the level of PI(4,5)P2 was decreased with a corresponding increase in the level of the substrate PI(4)P. Reintroduction of Ajuba into these cells normalized PI(4,5)P2 levels. Localization of PI(4,5)P2 synthesis and PIPKIalpha in the leading lamellipodia and membrane ruffles, respectively, of migrating Ajuba(-/-) MEFs was impaired. In vitro, Ajuba dramatically activated the enzymatic activity of PIPKIalpha while inhibiting the activity of PIPKIIbeta. Thus, in addition to its effects upon Rac activity Ajuba can also influence cell migration through regulation of PI(4,5)P2 synthesis through direct activation of PIPKIalpha enzyme activity.
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