Abstract
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.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Analysis of Variance
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Androstadienes / pharmacology
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Animals
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Apoptosis*
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Blotting, Western
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Brain / cytology
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Brain / drug effects
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Brain / metabolism
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Carrier Proteins / metabolism*
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Cell Fractionation / methods
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Cells, Cultured
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Cloning, Molecular / methods
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DNA Fragmentation / physiology
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / pharmacology
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Homer Scaffolding Proteins
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Humans
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Immunohistochemistry
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In Vitro Techniques
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Kidney
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Leucine / genetics
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Molecular Sequence Data
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Mutation
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Nerve Tissue Proteins / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / virology
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Neuropeptides / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism*
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Precipitin Tests / methods
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Proline / genetics
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Protein Binding / physiology
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Proteins / metabolism
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Proto-Oncogene Proteins c-myc / metabolism
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Pyridines / pharmacology
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Quisqualic Acid / pharmacology
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RNA, Messenger / biosynthesis
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Rats
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Receptors, Metabotropic Glutamate / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Staurosporine / pharmacology
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Subcellular Fractions / metabolism
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Synaptophysin / metabolism
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Transfection
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Wortmannin
Substances
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Androstadienes
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Carrier Proteins
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Homer Scaffolding Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Proteins
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Proto-Oncogene Proteins c-myc
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Pyridines
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RNA, Messenger
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Receptors, Metabotropic Glutamate
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Synaptophysin
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metabotropic glutamate receptor type 1
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postsynaptic density proteins
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Glutamic Acid
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6-methyl-2-(phenylethynyl)pyridine
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Quisqualic Acid
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Proline
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PARP1 protein, human
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Parp1 protein, rat
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Phosphatidylinositol 3-Kinases
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Leucine
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Staurosporine
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Wortmannin
Associated data
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GENBANK/AY128688
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GENBANK/AY128689