JBC Focus on PI3-Kinase with Echelon

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Originally published In Press as doi:10.1074/jbc.M502318200 on May 24, 2005 Originally published In Press as doi:10.1074/jbc.M502318200 on May 23, 2005

J. Biol. Chem., Vol. 280, Issue 29, 26845-26855, July 22, 2005
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Cross-talk between JIP3 and JIP1 during Glucose Deprivation

SEK1-JNK2 AND Akt1 ACT AS MEDIATORS*{boxs}

Jae J. Song and Yong J. Lee{ddagger}

From the Department of Surgery and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

We have previously observed that glucose deprivation activates the ASK1-MEK-MAPK signal transduction pathway. In the present study, we reveal that two scaffolding proteins, JIP1 and JIP3, have a cross-talk that leads to the regulation of the ASK1-SEK1-JNK signal during glucose deprivation. Glucose deprivation rapidly increases the interaction between ASK1 and JIP3, and the consequently activated ASK1 phosphorylates SEK1 on the Thr-261 residue. The activated SEK1 dissociates from JIP3 and phosphorylates JNK2 on the Tyr-185 residue. Phosphorylated JNK2 binds to JIP1, and the phosphorylation of the Thr-183 residue of JNK2 occurs. JNK2 phosphorylates JIP1 on the Thr-103 residue and leads to dissociation of Akt1 from JIP1. Dissociated Akt1 binds to SEK1 and ASK1 and inhibits their enzyme activity by phosphorylating SEK1 on the Ser-80 residue and ASK1 on the Ser-83 residue. Taken together, our data demonstrate that cross-talk between JIP3 and JIP1 is mediated through SEK1-JNK2 and Akt1.


Received for publication, March 1, 2005 , and in revised form, May 19, 2005.

* This work was supported by NCI, National Institutes of Health Grants CA95191 and CA96989, the Elsa U. Pardee Foundation, the Pittsburgh Foundation, and Department of Defense prostate program fund Grant PC020530. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains an additional figure.

{ddagger} To whom all correspondence should be addressed: Dept. of Surgery, University of Pittsburgh, Hillman Cancer Center, 5117 Centre Ave., Rm. 1.19, Pittsburgh, PA 15213. Tel.: 412-623-3268; Fax: 412-623-1010; E-mail: leeyj{at}msx.upmc.edu.


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