NDLI: The tyrosine phosphatase Shp-2 interacts with the dopamine D1 receptor and triggers D1-mediated Erk signaling in striatal neurons

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The tyrosine phosphatase Shp-2 interacts with the dopamine D1 receptor and triggers D1-mediated Erk signaling in striatal neurons

Content Provider	Scilit
Author	Fiorentini, Chiara Mattanza, Cinzia Collo, Ginetta Savoia, Paola Spano, Pierfranco Missale, Cristina
Copyright Year	2011
Description	Journal: Journal of Neurochemistry We report a novel mechanism for dopamine D(1) receptor (D(1) R)-mediated extracellular signal-regulated kinases (Erk) activation in rat striatum. Erk signaling depends on phosphorylation and dephosphorylation events mediated by specific kinases and phosphatases. The tyrosine phosphatase Shp-2, that is required for Erk activation by tyrosine kinase receptors, has been recently shown to regulate signaling downstream of few G protein-coupled receptors. We show that the D(1) R interacts with Shp-2, that D(1) R stimulation results in Shp-2 tyrosine phosphorylation and activation in primary striatal neuronal cultures and that D(1) R/Shp-2 interaction is required for transmitting D(1) R-dependent signaling to Erk1/2 activation. D(1) R-mediated Erk1/2 phosphorylation in cultured striatal neurons is in fact abolished by over-expression of the inactive Shp-2(C/S) mutant and by small interfering RNA-induced Shp-2 silencing. Moreover, by using selective inhibitors we show that both D(1) R-induced Shp-2 activation and Erk1/2 phosphorylation are dependent on the cyclic AMP/protein kinase A pathway and require Src. These results, which were substantiated also in transfected human embryonic kidney 293 cells, provide a novel mechanism by which to converge D(1) R signaling to the Erk pathway and suggest that Shp-2 or the D(1) R/Shp-2 interface could represent a potential drug target for disorders of dopamine transmission involving malfunctioning of D(1) R signaling.
Related Links	http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2011.07196.x/pdf
Ending Page	263
Page Count	11
Starting Page	253
e-ISSN	14714159
DOI	10.1111/j.1471-4159.2011.07196.x
Journal	Journal of Neurochemistry
Issue Number	2
Volume Number	117
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2011-02-24
Access Restriction	Open
Subject Keyword	Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Cyclic Amp Dopamine Receptors Protein Kinase A Rna Silencing Striatal Cultures
Content Type	Text
Resource Type	Article

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