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A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II

Chen, Hong Jung and Rojas-Soto, Michelle and Oguni, Asako and Kennedy, Mary B. (1998) A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II. Neuron, 20 (5). pp. 895-904. ISSN 0896-6273. http://resolver.caltech.edu/CaltechAUTHORS:20120424-150615407

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Abstract

Ca^(2+) influx through N-methyl-D-aspartate– (NMDA–) type glutamate receptors plays a critical role in synaptic plasticity in the brain. One of the proteins activated by the increase in Ca^(2+) is CaM kinase II (CaMKII). Here, we report a novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major component of the postsynaptic density, a complex of proteins associated with synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses in hippocampal neurons where it binds to and closely colocalizes with the scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0896-6273(00)80471-7DOIUNSPECIFIED
http://www.sciencedirect.com/science/article/pii/S0896627300804717PublisherUNSPECIFIED
Additional Information:© 1998 by Cell Press. Received March 26, 1998; revised April 13, 1998. Available online 25 September 2000. We thank L. Schenker for technical assistance and Gary Hathaway and Dirk Krapf of the Caltech microsequencing facility for mass spectrometric measurements and amino acid sequences. This work was supported by U.S. Public Health Service grants NS-28710 and 17660. A preliminary report of these findings was published in abstract form: Chen, H.-J., and Kennedy, M. B. (1997, Soc. Neurosci., abstract).
Funders:
Funding AgencyGrant Number
U.S. Public Health Service (USPHS)NS-28710
U.S. Public Health Service (USPHS)NS-17660
Record Number:CaltechAUTHORS:20120424-150615407
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120424-150615407
Official Citation:Hong-Jung Chen, Michelle Rojas-Soto, Asako Oguni, Mary B Kennedy, A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II, Neuron, Volume 20, Issue 5, May 1998, Pages 895-904, ISSN 0896-6273, 10.1016/S0896-6273(00)80471-7. (http://www.sciencedirect.com/science/article/pii/S0896627300804717)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30311
Collection:CaltechAUTHORS
Deposited By: Melanie Stefan
Deposited On:26 Apr 2012 16:02
Last Modified:26 Apr 2012 16:02

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