K252a and CEP1347 Are Neuroprotective Compounds That Inhibit Mixed-lineage Kinase-3 and Induce Activation of Akt and ERK

• Published in: The Journal of biological chemistry Vol. 277; no. 51; pp. 49473 - 49480
• Main Authors: Roux, Philippe P., Dorval, Geneviève, Boudreau, Mathieu, Angers-Loustau, Alexandre, Morris, Stephen J., Makkerh, Joe, Barker, Philip A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.12.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Adenoviridae - genetics; Animals; Carbazoles - pharmacology; Cell Line; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors - pharmacology; Indole Alkaloids; Indoles - pharmacology; Inhibitory Concentration 50; MAP Kinase Kinase Kinases - antagonists & inhibitors; Mice; Mitogen-Activated Protein Kinase Kinase Kinase 11; Mitogen-Activated Protein Kinases - metabolism; Models, Chemical; Neurons - cytology; Neurons - metabolism; Neuroprotective Agents - pharmacology; PC12 Cells; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Precipitin Tests; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Recombinant Proteins - metabolism; Signal Transduction; Time Factors

K252a is best known as a Trk inhibitor, but is also a neuroprotective compound. CEP1347, a K252a derivative, retains neuroprotective properties, but does not inhibit TrkA. CEP1347 has recently been shown to directly inhibit MAPKKKs, including MLK3, but the effect of K252a on MAPKKKs remains unknown....