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Insulin-Induced Dephosphorylation of C/EBPα

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Science's STKE  07 Dec 1999:
Vol. 1999, Issue 11, pp. tw3
DOI: 10.1126/stke.1999.11.tw3

The transcription factor C/EBPα is critical for normal adipose tissue development and metabolism. When it is inhibited or not expressed, adipocytes fail to take up glucose in response to insulin. In normal adipocytes, insulin causes a decrease in the expression, activity, and phosphorylation of C/EBPα. Ross et al. demonstrate that two threonine residues in a conserved region of this transcription factor are phosphorylated by a glycogen synthase kinase (GSK3) in vivo and in vitro. Dephosphorylation of C/EBPα not only involved inactivation of GSK3, but also the activation of the protein phosphatases PP1 and PP2A, enzymes known to be activated by insulin. Hence, a decrease in the phosphorylation of this transcription factor in response to insulin involves two mechanisms. Phosphorylation also altered accessibility of C/EBPα to proteases, suggesting that its state of phosphorylation may regulate interaction with other nuclear proteins or transcriptional coactivators. However, the precise role of this modification remains to be determined. The report suggests a signaling mechanism in adipocytes through which C/EBPα is regulated by insulin.

Ross, S.E., Erickson, R.L., Hemati, N., and MacDougald, O.A. (1999) Glycogen synthase kinase 3 is an insulin-regulated C/EBPα kinase. Mol. Cell. Biol. 19: 8433-8441. [Online Journal]

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