PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis.
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 (mGluRIs) enhances formation of an mGluRI-Homer-PIKE-L 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 mGluRI to prevent neuronal apoptosis.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adenoviridae, Amino Acid Motifs, Amino Acid Sequence, Analysis of Variance, Androstadienes, Animals, Apoptosis, Blotting, Western, Brain, Carrier Proteins, Cell Fractionation, Cells, Cultured, Cloning, Molecular, DNA Fragmentation, Embryo, Mammalian, Enzyme Inhibitors, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Glutamic Acid, Humans, Immunohistochemistry, Kidney, Leucine, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Neuropeptides, Poly(ADP-ribose) Polymerases, Precipitin Tests, Proline, Protein Binding, Proteins, Proto-Oncogene Proteins c-myc, Pyridines, Quisqualic Acid, RNA, Messenger, Rats, Receptors, Metabotropic Glutamate, Reverse Transcriptase Polymerase Chain Reaction, Staurosporine, Subcellular Fractions, Synaptophysin, Transfection
1-Phosphatidylinositol 3-Kinase, Adenoviridae, Amino Acid Motifs, Amino Acid Sequence, Analysis of Variance, Androstadienes, Animals, Apoptosis, Blotting, Western, Brain, Carrier Proteins, Cell Fractionation, Cells, Cultured, Cloning, Molecular, DNA Fragmentation, Embryo, Mammalian, Enzyme Inhibitors, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Glutamic Acid, Humans, Immunohistochemistry, Kidney, Leucine, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Neuropeptides, Poly(ADP-ribose) Polymerases, Precipitin Tests, Proline, Protein Binding, Proteins, Proto-Oncogene Proteins c-myc, Pyridines, Quisqualic Acid, RNA, Messenger, Rats, Receptors, Metabotropic Glutamate, Reverse Transcriptase Polymerase Chain Reaction, Staurosporine, Subcellular Fractions, Synaptophysin, Transfection
Nat. Neurosci.
Date: Nov. 01, 2003
PubMed ID: 14528310
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