JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
Open accessAbstract
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.
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JIP-1, JIP-2, and JIP-3 are scaffolding proteins for the JNK signaling pathway.
“Three proteins were found, the c-jun NH2-terminal kinase (JNK)–interacting proteins (JIPs) JIP-1, JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway.”
From Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules (2001) · cites this paper as Ito et al. 1999
JIP-3 can form oligomeric complexes with itself and JIP-2 but has no sequence relationship to JIP-1 or JIP-2.
“JIP-3 (also known as JSAP) can form oligomeric complexes with itself and JIP-2 but has no sequence relationship to JIP-1 or JIP-2 (Ito et al. 1999; Kelkar et al. 2000).”
From Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules (2001) · cites this paper as Ito et al. 1999
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- Authors
- Ito, M., Yoshioka, K., Akechi, M., Yamashita, S., Takamatsu, N., Sugiyama, K., Hibi, M., Nakabeppu, Y., Shiba, T., & Yamamoto, K.-I.
- Affiliations
- Kitasato University (JP)
- Kanazawa University (JP)
- Nippon Suisan Kaisha (Japan) (JP)
- Nippon Boehringer Ingelheim Co., Ltd., Kawanishi Pharma Research Institute, Department of Molecular and Cellular Biology
- The University of Osaka (JP)
- Kyushu University (JP)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-11
- Volume
- 19
- Issue
- 11
- Pages
- 7539-7548
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84763
- OpenAlex
- W2140851951
- Cited by
- 279
- References
- 55
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 5 · 2012: 6
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Waksman Foundation of Japan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- JNK signaling, scaffold proteins, MEKK1, SEK1, MAPK signaling, protein-protein interaction, MAPK kinase kinase, MAPK kinase, Raf-1, MEK1, c-Jun N-terminal kinase, JNK1, JNK2
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cloning, Molecular, Enzyme Activation, Molecular Sequence Data, Nerve Tissue Proteins, Phosphorylation, Protein Binding, Protein Kinases, Protein-Tyrosine Kinases, Protein Serine-Threonine Kinases, Two-Hybrid System Techniques, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinase 10, MAP Kinase Kinase 4, MAP Kinase Kinase Kinase 1, Adaptor Proteins, Signal Transducing, Mice
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