Abstract |
My laboratory recently demonstrated that there is selective expression of phosphoribosomal S6 protein in balloon cells in focal cortical dysplasia and hemimegalencephaly but no expression of the upstream kinase, phospho-p70S6 kinase. Two proteins activated by phospho-p70S6 kinase, phospho-STAT3 and phospho-4EBP1, were not detected in balloon cells. Using complementary DNA arrays in hemimegalencephaly specimens, we found increased expression of cyclin D1 and c-myc messenger ribonucleic acids (RNAs). Expression of cyclin D1 and c-myc genes is transcriptionally activated by beta-catenin. Western analysis demonstrated increased levels of nonphosphorylated beta-catenin in hemimegalencephalic cortex. Reduced levels of Ser33, Ser37, and Thr41 phospho- beta-catenin, sites known to be phosphorylated by glycogen synthase kinase 3 and to be essential for beta-catenin inactivation, were detected in hemimegalencephaly. Enhanced transcription of cyclin D1 and c-myc messenger RNAs, increased transcriptionally active beta-catenin, and decreased Ser33/Ser37/Thr41 phospho- beta-catenin suggest activation of the Wnt-1/ beta-catenin cascade in hemimegalencephaly, which can lead to aberrant cell proliferation and hemispheric enlargement during brain development. Enhanced activation of phospho-S6 and beta-catenin suggests two converging cell pathways that can be pivotal in the pathogenesis of focal cortical dysplasia and hemimegalencephaly.
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Authors | Peter B Crino |
Journal | Journal of child neurology
(J Child Neurol)
Vol. 20
Issue 4
Pg. 330-6
(Apr 2005)
ISSN: 0883-0738 [Print] United States |
PMID | 15921235
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- CTNNB1 protein, human
- Cytoskeletal Proteins
- Intercellular Signaling Peptides and Proteins
- RNA, Messenger
- Trans-Activators
- WNT1 protein, human
- Wnt Proteins
- Wnt1 Protein
- beta Catenin
- Protein Kinases
- MTOR protein, human
- Ribosomal Protein S6 Kinases, 70-kDa
- TOR Serine-Threonine Kinases
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Topics |
- Adolescent
- Adult
- Case-Control Studies
- Cerebral Cortex
(abnormalities, metabolism)
- Child
- Child, Preschool
- Cytoskeletal Proteins
(genetics, metabolism)
- Epilepsy
(genetics, metabolism, pathology)
- Female
- Humans
- Infant
- Intercellular Signaling Peptides and Proteins
(genetics, metabolism)
- Male
- Nervous System Malformations
(genetics, metabolism, pathology)
- Protein Kinases
(metabolism)
- RNA, Messenger
(metabolism)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- Signal Transduction
(physiology)
- TOR Serine-Threonine Kinases
- Trans-Activators
(genetics, metabolism)
- Wnt Proteins
- Wnt1 Protein
- beta Catenin
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