Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation

doi:10.1128/MCB.20.7.2334-2342.2000

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Molecular and Cellular Biology, April 2000, p. 2334-2342, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation

Jinke Cheng,¹ Jianhua Yang,¹ Ying Xia,² Michael Karin,² and Bing Su¹^,^*

Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030,¹ and Department of Pharmacology, University of California at San Diego, La Jolla, California 92093²

Received 21 September 1999/Returned for modification 2 November 1999/Accepted 29 January 2000

Mitogen-activated protein kinases (MAPKs) are activated through cascades or modules consisting of a MAPK, a MAPK kinase (MAPKK),and a MAPKK kinase (MAPKKK). Investigating the molecular basisof activation of the c-Jun N-terminal kinase (JNK) subgroup ofMAPK by the MAPKKK MEKK2, we found that strong and specific JNK1activation by MEKK2 was mediated by the MAPKK JNK kinase 2 (JNKK2)rather than by JNKK1 through formation of a tripartite complexconsisting of MEKK2, JNKK2, and JNK1. No scaffold protein wasrequired for the MEKK2-JNKK2-JNK1 tripartite-complex formation.Expression of JNK1, JNKK2, and MEKK2 significantly augmented thecoprecipitation of, respectively, MEKK2-JNKK2, MEKK2-JNK1, andJNKK2-JNK1, indicating that the interaction of MEKK2, JNKK2, andJNK1 is synergistic. Finally, the JNK1 was activated more efficientlyin the MEKK2-JNKK2-JNK1 complex than was the JNK1 excluded fromthe complex. Thus, formation of a signaling complex through synergisticinteraction of a MAPKKK, a MAPKK, and a MAPK molecule like MEKK2-JNKK2-JNK1is likely to be responsible for the efficient, specific flow ofinformation via MAPKcascades.

^* Corresponding author. Mailing address: Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, 1515Holcombe Blvd., Houston, TX 77030. Phone: (713) 792-8742. Fax:(713) 745-1633. E-mail: bingsu{at}odin.mdacc.tmc.edu.

Molecular and Cellular Biology, April 2000, p. 2334-2342, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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