MEKK1 Binds Raf-1 and the ERK2 Cascade Components*
- From the Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041
Abstract
Mitogen-activated protein (MAP) kinase cascades are involved in transmitting signals that are generated at the cell surface into the cytosol and nucleus and consist of three sequentially acting enzymes: a MAP kinase, an upstream MAP/extracellular signal-regulated protein kinase (ERK) kinase (MEK), and a MEK kinase (MEKK). Protein-protein interactions within these cascades provide a mechanism to control the localization and function of the proteins. MEKK1 is implicated in activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and ERK1/2 MAP kinase pathways. We showed previously that MEKK1 binds directly to JNK/SAPK. In this study we demonstrate that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK2 MAP kinase module.
Footnotes
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↵* This work was supported by Grants GM56498 and DK34128 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Supported in part by a fellowship from the Perot Family Foundation.
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↵§ Present address: Salk Institute; La Jolla, CA.
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↵¶ To whom correspondence should be addressed: Dept. of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9041. E-mail: mcobb@mednet.swmed. edu.
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Published, JBC Papers in Press, August 31, 2000, DOI 10.1074/jbc.M005926200
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↵2 M. Karandikar, J. R. Woodgett, and M. H. Cobb, submitted for publication.
- Abbreviations:
- MAP
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mitogen-activated protein
- ERK
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extracellular signal-regulated protein kinase
- MEK
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MAP kinase/ERK kinase (also called MAP kinase kinase or MKK)
- MEKK1
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MEK kinase 1
- JNK
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c-Jun N-terminal kinase
- SAPK
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stress-activated protein kinase
- GST
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glutathioneS-transferase
- HA hemagglutinin
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CAL, calmodulin-binding protein
- PKA
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cAMP-dependent protein kinase
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- Received July 6, 2000.
- Revision received August 7, 2000.
- The American Society for Biochemistry and Molecular Biology, Inc.
