Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles.

We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.

Citation

Eijiro Yamada, Shuichi Okada, Tsugumichi Saito, Kihachi Ohshima, Minoru Sato, Takafumi Tsuchiya, Yutaka Uehara, Hiroyuki Shimizu, Masatomo Mori. Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. The Journal of cell biology. 2005 Mar 14;168(6):921-8

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PMID: 15753124

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