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J. Biol. Chem., Vol. 276, Issue 19, 16070-16075, May 11, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/19/16070    most recent M100681200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Z. Articles by Cobb, M. H. Search for Related Content PubMed PubMed Citation Articles by Chen, Z. Articles by Cobb, M. H. Social Bookmarking                      What's this?

Regulation of Stress-responsive Mitogen-activated Protein (MAP) Kinase Pathways by TAO2^*

Zhu Chen and Melanie H. Cobb^§

From the Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041

Previous studies demonstrated that in vitro the protein kinase TAO2 activates MAP/ERK kinases (MEKs) 3, 4, and 6 toward their substrates p38 MAP kinase and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). In this study, we examined the ability of TAO2 to activate stress-sensitive MAP kinase pathways in cells and the relationship between activation of TAO2 and potential downstream pathways. Over-expression of TAO2 activated endogenous JNK/SAPK and p38 but not ERK1/2. Cotransfection experiments suggested that TAO2 selectively activates MEK3 and MEK6 but not MEKs 1, 4, or 7. Coimmunoprecipitation demonstrated that endogenous TAO2 specifically associates with MEK3 and MEK6 providing one mechanism for preferential recognition of MEKs upstream of p38. Sorbitol, and to a lesser extent, sodium chloride, Taxol, and nocodazole increased TAO2 activity toward itself and kinase-dead MEKs 3 and 6. Activation of endogenous TAO2 during differentiation of C2C12 myoblasts paralleled activation of p38 but not JNK/SAPK, consistent with the idea that TAO2 is a physiological regulator of p38 under certain circumstances.

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