PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis

Academic Article


  • Phosphoinositide 3 kinase enhancer (PIKE) is a recently identified nuclear GTPase that activates nuclear phosphoinositide 3-kinase (PI3 kinase). We have identified, cloned and characterized a new form of PIKE, designated PIKE-L, which, unlike the nuclear PIKE-S, localizes to both the cytoplasm and the nucleus. We demonstrate physiologic binding of PIKE-L to Homer, an adaptor protein known to link metabotropic glutamate receptors to multiple intracellular targets including the inositol 1,4,5-trisphosphate receptor (IP3R). We show that activation of group I metabotropic glutamate receptors (mGluR1s) enhances formation of an mGluR1-Homer complex, leading to activation of PI3 kinase activity and prevention of neuronal apoptosis. Our findings indicate that this complex mediates the well-known ability of agonists of mGluR1 to prevent neuronal apoptosis.
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    Author List

  • Rong R; Ahn JY; Huang H; Nagata E; Kalman D; Kapp JA; Tu J; Worley PF; Snyder SH; Ye K
  • Start Page

  • 1153
  • End Page

  • 1161
  • Volume

  • 6
  • Issue

  • 11