title: Reassembly of JIP1 scaffold complex in JNK MAP kinase pathway using heterologous protein interactions.
abstract: Formation of signaling protein complexes is crucial for proper signal transduction. Scaffold proteins in MAP kinase pathways are thought to facilitate complex assembly, thereby promoting efficient and specific signaling. To elucidate the assembly mechanism of scaffold complexes in mammals, we attempted to rationally rewire JIP1-dependent JNK MAP kinase pathway via alternative assembly of JIP1 complex. When JIP1-JNK docking interaction in the complex was replaced with heterologous protein interaction domains, such as PDZ domains and JNK-binding domains, a functional scaffold complex was reconstituted, and JNK signaling was rescued. Reassembly of JIP1 complex using heterologous protein interactions was sufficient for restoring of JNK MAP kinase pathway to induce signaling responses, including JNK activation and cell death. These results suggest a simple yet modular mechanism for JIP1 scaffold assembly in mammals.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D009154:Mutation; D054731:PDZ Domains; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases