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PMA activates Stat3 in the Jak/Stat pathway and induces SOCS5 in rat brain astrocytes.

Hwang, MN; Kim, KS; Choi, YW; Jou, I; Yoon, S
Molecules and cells, 23(1):94-99, 2007
Journal Title
Molecules and cells
Suppressors of cytokine signaling (SOCS) family members are negative feedback regulators of the Jak/Stat pathway, which is an essential inflammatory signaling pathway. We investigated expression of eight members of the SOCS family in rat astrocytes, using two inflammatory stimulants, PMA and IFN-gamma. Only a few SOCS genes were induced by both stimulants, and we detected an increase in SOCS5 protein with PMA. PMA activated the Jnk, Erk, p38, and Jak/Stat signal pathways. In addition, it increased the level of activated-Stat3 resulting from tyrosine phosphorylation. A gel-shift assay showed that a protein in nuclear extracts from PMA-treated cells was able to bind to Stat binding elements. These results suggest that activated Stat3 binds to SOCS promoters and leads to their transcriptional induction.
MeSH terms
AnimalsAstrocytes/cytologyAstrocytes/drug effectsAstrocytes/metabolism*Brain/cytology*Brain/drug effectsBrain/metabolismEnzyme Activation/drug effectsExtracellular Signal-Regulated MAP Kinases/metabolismGene Expression Regulation/drug effects*InflammationInterferon-gamma/pharmacologyJNK Mitogen-Activated Protein Kinases/metabolismJanus Kinases/metabolism*MAP Kinase Signaling System/drug effectsPhosphorylation/drug effectsPhosphotyrosine/metabolismProtein Binding/drug effectsProto-Oncogene Proteins pp60(c-src)/metabolismRatsRats, Sprague-DawleyResponse Elements/drug effectsSTAT3 Transcription Factor/metabolism*Suppressor of Cytokine Signaling Proteins/genetics*Suppressor of Cytokine Signaling Proteins/metabolismTetradecanoylphorbol Acetate/pharmacology*p38 Mitogen-Activated Protein Kinases/metabolism
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