Activation of Akt/PDK signaling in macrophages upon binding of receptor-recognized forms of α2-macroglobulin to its cellular receptor: Effect of silencing the CREB gene
✍ Scribed by U.K. Misra; Salvatore V. Pizzo
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 403 KB
- Volume
- 93
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Macrophage binding of receptor-recognized forms of a 2 -macrogobulin (a 2 M*) significantly increases cAMP, CREB, and activated CREB. We have now examined the participation of the PI 3-kinase/PDK/Akt/p70s6k signaling cascade in a 2 M*-induced cellular proliferation and also studied the role of CREB in these events. Exposure of cells to a 2 M* caused an $2-fold increase in CREB and its phosphorylation at Ser 133 , phosphorylation of the regulatory subunit of PI 3-kinase, Akt phosphorylation at Ser 473 or Thr 308 , and phosphorylated 70s6k. Silencing of the CREB gene with dsRNA homologous in sequence to the target gene, markedly reduced the levels of CREB mRNA activation of CREB, PI 3-kinase, Akt, and p70s6k in a 2 M*-stimulated macrophages. We conclude that in murine peritoneal macrophages, a 2 M*-induced increase of cAMP is involved in cellular proliferation and this process is mediated by the PI 3-kinase signaling cascade.