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High-level expression of Dok-1 in neurons of the primate prefrontal cortex and hippocampus

✍ Scribed by A. Smith; J. Wang; C.M. Cheng; J. Zhou; C.S. Weickert; C.A. Bondy


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
515 KB
Volume
75
Category
Article
ISSN
0360-4012

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✦ Synopsis


Abstract

The docking protein p62Dok‐1 (Dok‐1) has a central role in cell signaling mediated by a wide range of protein tyrosine kinases, including intrinsic membrane kinases, such as the insulin‐like growth factor‐1 (IGF‐1) receptor. To elucidate potential IGF signaling mechanisms, we used DNA array technology to investigate novel kinase targets expressed in the primate dorsolateral prefrontal cortex (DLPFC). Dok‐1 transcripts were among the most abundant found in this structure. Because Dok‐1 expression has not been characterized in brain, we evaluated its expression pattern using immunoblotting, in situ hybridization, and immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal formation. Dok‐1 antibodies identified a 62‐kDa band in lysates from the DLPFC, consistent with the known size for Dok‐1. In situ hybridization showed that Dok‐1 mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation. Immunohistochemical analysis showed Dok‐1 immunoreactivity concentrated in pyramidal neurons of cortical layers IV–V and throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok‐1 expression was also identified in endothelial cells of cerebral blood vessels. These expression patterns are very similar to those of the IGF‐1 receptor and suggest that Dok‐1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory. Published 2003 Wiley‐Liss, Inc.


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