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Molecular and Cellular Biology, November 1999, p. 7539-7548, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway

Michihiko Ito,1 Katsuji Yoshioka,2,* Mizuho Akechi,1 Shinya Yamashita,3 Nobuhiko Takamatsu,1 Kenji Sugiyama,4 Masahiko Hibi,5 Yusaku Nakabeppu,6 Tadayoshi Shiba,1 and Ken-Ichi Yamamoto2

Department of Biosciences, School of Science, Kitasato University, Kanagawa 228,1 Department of Molecular Pathology, Cancer Research Institute, Kanazawa University, Kanazawa 920,2 Central Research Laboratory, Nippon Suisan Kaisha Ltd., Tokyo 192,3 Nippon Boehringer Ingelheim Co., Ltd., Kawanishi Pharma Research Institute, Department of Molecular and Cellular Biology, Hyogo 666,4 Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Osaka 565,5 and Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology, Fukuoka 812,6 Japan

Received 17 June 1999/Returned for modification 28 July 1999/Accepted 12 August 1999

The major components of the mitogen-activated protein kinase (MAPK) cascades are MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). Recent rapid progress in identifying members of MAPK cascades suggests that a number of such signaling pathways exist in cells. To date, however, how the specificity and efficiency of the MAPK cascades is maintained is poorly understood. Here, we have identified a novel mouse protein, termed Jun N-terminal protein kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), by a yeast two-hybrid screen, using JNK3 MAPK as the bait. Of the mammalian MAPKs tested (JNK1, JNK2, JNK3, ERK2, and p38alpha ), JSAP1 preferentially coprecipitated with the JNKs in cotransfected COS-7 cells. JNK3 showed a higher binding affinity for JSAP1, compared with JNK1 and JNK2. In similar cotransfection studies, JSAP1 also interacted with SEK1 MAPKK and MEKK1 MAPKKK, which are involved in the JNK cascades. The regions of JSAP1 that bound JNK, SEK1, and MEKK1 were distinct from one another. JNK and MEKK1 also bound JSAP1 in vitro, suggesting that these interactions are direct. In contrast, only the activated form of SEK1 associated with JSAP1 in cotransfected COS-7 cells. The unstimulated SEK1 bound to MEKK1; thus, SEK1 might indirectly associate with JSAP1 through MEKK1. Although JSAP1 coprecipitated with MEK1 MAPKK and Raf-1 MAPKKK, and not MKK6 or MKK7 MAPKK, in cotransfected COS-7 cells, MEK1 and Raf-1 do not interfere with the binding of SEK1 and MEKK1 to JSAP1, respectively. Overexpression of full-length JSAP1 in COS-7 cells led to a considerable enhancement of JNK3 activation, and modest enhancement of JNK1 and JNK2 activation, by the MEKK1-SEK1 pathway. Deletion of the JNK- or MEKK1-binding regions resulted in a significant reduction in the enhancement of the JNK3 activation in COS-7 cells. These results suggest that JSAP1 functions as a scaffold protein in the JNK3 cascade. We also discuss a scaffolding role for JSAP1 in the JNK1 and JNK2 cascades.

* Corresponding author. Mailing address: Department of Molecular Pathology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-0934, Japan. Phone: 81-76-265-2757. Fax: 81-76-234-4517. E-mail: katsuji{at}kenroku.kanazawa-u.ac.jp.

Molecular and Cellular Biology, November 1999, p. 7539-7548, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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  • Abe, Y., Matsumoto, S., Kito, K., Ueda, N. (2000). Cloning and Expression of a Novel MAPKK-like Protein Kinase, Lymphokine-activated Killer T-cell-originated Protein Kinase, Specifically Expressed in the Testis and Activated Lymphoid Cells. J. Biol. Chem. 275: 21525-21531 [Abstract] [Full Text]  
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