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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | He, Zhigang Harrington, Anthony W. Tep, Chhavy Park, Jong Bae Li, Qi Ming Yoon, Sung Ok |
| Description | Author Affiliation: Harrington AW ( Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, The Ohio State University, Columbus, Ohio 43210, USA.) |
| Abstract | p75 and the Nogo receptor form a signaling unit for myelin inhibitory molecules, with p75 being responsible for RhoA activation. Because p75 lacks the GDP/GTP exchange factor domain, it has remained unclear how p75 activates RhoA. Here, we report that Kalirin9, a dual RhoGEF, binds p75 directly and regulates p75-Nogo receptor-dependent RhoA activation and neurite inhibition in response to myelin-associated glycoprotein. The region of p75 that Kalirin9 binds includes its mastoparan-like fifth helix, which was shown to recruit RhoGDI-RhoA. As predicted from the presence of a shared binding site, we found that Kalirin9 competes with RhoGDI for p75 binding in a dose-dependent manner in vitro. In line with these data, myelin-associated glycoprotein addition to cerebellar granule neurons resulted in a reduction in the association of Kalirin9 with p75, and a simultaneous increase in the binding of RhoGDI to p75. These results reveal a mechanism by which the fifth helix of p75 regulates RhoA activation. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 36 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-09-05 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cerebellum Metabolism Guanine Nucleotide Exchange Factors Neurites Receptors, Nerve Growth Factor Receptors, Peptide RhoA GTP-Binding Protein Animals Cell Line Cytology GPI-Linked Proteins Guanine Nucleotide Dissociation Inhibitors Myelin Proteins Myelin-Associated Glycoprotein Protein Structure, Secondary Physiology Protein Structure, Tertiary Receptors, Cell Surface Rho Guanine Nucleotide Exchange Factors Rho-Specific Guanine Nucleotide Dissociation Inhibitors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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