Abstract | BACKGROUND: METHODS: The authors assessed endogenous CREB phosphorylation in a CLS fibroblast line by Western blotting and found impaired CREB phosphorylation in response to stimulation by EGF and the protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate (PMA). They studied RSK2 immunoprecipitated from fibroblasts and lymphoblasts from seven patients with CLS and found a wide range in RSK2's capacity to phosphorylate the synthetic CREB-like peptide, CREBtide, after cell stimulation by PMA. RESULTS: In lymphoblasts from patients with CLS, PMA-stimulated CREBtide phosphorylation was increased 1.2- to 2.7-fold over baseline, compared to an average fourfold increase in controls. Regression analysis suggested a linear relationship between the magnitude of in vitro RSK2-mediated CREBtide phosphorylation and CLS patient intelligence level (p < 0.05). CONCLUSIONS: This report suggests a correlation between human cognitive performance and cellular capacity to activate RSK2. It provides additional evidence that the CREB kinase, RSK2, and CREB phosphorylation may play important roles in human learning and memory, as they do in lower animals.
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Authors | K H Harum, L Alemi, M V Johnston |
Journal | Neurology
(Neurology)
Vol. 56
Issue 2
Pg. 207-14
(Jan 23 2001)
ISSN: 0028-3878 [Print] United States |
PMID | 11160957
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cyclic AMP Response Element-Binding Protein
- Ribosomal Protein S6 Kinases
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Topics |
- Abnormalities, Multiple
(enzymology, physiopathology)
- Child
- Child, Preschool
- Cognition Disorders
(enzymology, physiopathology)
- Cyclic AMP Response Element-Binding Protein
(metabolism)
- Female
- Humans
- Infant
- Intellectual Disability
(enzymology, physiopathology)
- Male
- Ribosomal Protein S6 Kinases
(metabolism)
- Syndrome
- X Chromosome
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