High-level expression of Dok-1 in neurons of the primate prefrontal cortex and hippocampus.
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.
Smith
A
A
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland.
Wang
J
J
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland.
Cheng
C M
CM
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland.
Zhou
J
J
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland.
Weickert
C S
CS
National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Bondy
C A
CA
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland.
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008253:Macaca mulatta / Q000033:anatomy & histology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D004268:DNA-Binding Proteins; C074561:GAP-associated protein p62; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1