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Activation of Akt/PDK signaling in macrophages upon binding of receptor‐recognized forms of α 2 ‐macroglobulin to its cellular receptor: Effect of silencing the CREB gene
Author(s) -
Misra U.K.,
Pizzo Salvatore V.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20233
Subject(s) - creb , protein kinase b , phosphorylation , microbiology and biotechnology , gene silencing , signal transduction , kinase , biology , chemistry , cancer research , gene , transcription factor , biochemistry
Macrophage binding of receptor‐recognized forms of α 2 ‐macrogobulin (α 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 α 2 M*‐induced cellular proliferation and also studied the role of CREB in these events. Exposure of cells to α 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 α 2 M*‐stimulated macrophages. We conclude that in murine peritoneal macrophages, α 2 M*‐induced increase of cAMP is involved in cellular proliferation and this process is mediated by the PI 3‐kinase signaling cascade. © 2004 Wiley‐Liss, Inc.