| http://purl.uniprot.org/citations/19158303 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19158303 | http://www.w3.org/2000/01/rdf-schema#comment | "Although survival-promoting effects of insulin-like growth factor-1 (IGF-1) during neurogenesis are well characterized, mitogenic effects remain less well substantiated. Here, we characterize cell cycle regulators and signaling pathways underlying IGF-1 effects on embryonic cortical precursor proliferation in vitro and in vivo. In vitro, IGF-1 stimulated cell cycle progression and increased cell number without promoting cell survival. IGF-1 induced rapid increases in cyclin D1 and D3 protein levels at 4 h and cyclin E at 8 h. Moreover, p27(KIP1) and p57(KIP2) expression were reduced, suggesting downregulation of negative regulators contributes to mitogenesis. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway specifically underlies IGF-1 activity, because blocking this pathway, but not MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase), prevented mitogenesis. To determine whether mechanisms defined in culture relate to corticogenesis in vivo, we performed transuterine intracerebroventricular injections. Whereas blockade of endogenous factor with anti-IGF-1 antibody decreased DNA synthesis, IGF-1 injection stimulated DNA synthesis and increased the number of S-phase cells in the ventricular zone. IGF-1 treatment increased phospho-Akt fourfold at 30 min, cyclins D1 and E by 6 h, and decreased p27(KIP1) and p57(KIP2) expression. Moreover, blockade of the PI3K/Akt pathway in vivo decreased DNA synthesis and cyclin E, increased p27(KIP1) and p57(KIP2) expression, and prevented IGF-1-induced cyclin E mRNA upregulation. Finally, IGF-1 injection in embryos increased postnatal day 10 brain DNA content by 28%, suggesting a role for IGF-1 in brain growth control. These results demonstrate a mitogenic role for IGF-1 that tightly controls both positive and negative cell cycle regulators, and indicate that the PI3K/Akt pathway mediates IGF-1 mitogenic signaling during corticogenesis."xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.1700-08.2009"xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/author | "Mairet-Coello G."xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/author | "DiCicco-Bloom E."xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/author | "Tury A."xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/pages | "775-788"xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/title | "Insulin-like growth factor-1 promotes G(1)/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex."xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://purl.uniprot.org/core/volume | "29"xsd:string |
| http://purl.uniprot.org/citations/19158303 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19158303 |
| http://purl.uniprot.org/citations/19158303 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19158303 |
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| http://purl.uniprot.org/uniprot/#_Q791X1-mappedCitation-19158303 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19158303 |
| http://purl.uniprot.org/uniprot/#_Q8BP34-mappedCitation-19158303 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19158303 |
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