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- Title
PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis.
- Authors
Rong Rong; Jee-Yin Ahn; Honglian Huang; Nagata, Eiichiro; Kalman, Daniel; Kapp, Judith A.; Jiancheng Tu, Judith A.; Worley, Paul F.; Snyder, Solomon H.; Keqiang Ye
- 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.
- Subjects
PHOSPHOINOSITIDES; PROTEIN binding; CYTOPLASM; CELL nuclei
- Publication
Nature Neuroscience, 2003, Vol 6, Issue 11, p1153
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn1134