title: JNK2 is a positive regulator of the cJun transcription factor.
abstract: The cJun NH(2)-terminal kinase (JNK) signal transduction pathway is established to be an important mechanism of regulation of the cJun transcription factor. Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms have opposite effects on cJun expression and proliferation. Here, we demonstrate, using a chemical genetic approach, that both JNK1 and JNK2 are positive regulators of these processes. We show that competition between JNK1 and JNK2 contributes to the opposite phenotypes caused by JNK1 and JNK2 deficiency. Our analysis illustrates the power of a chemical genetics approach for the analysis of signal transduction pathways and also highlights the limitations of single gene knockout strategies for the analysis of signaling pathways that are formed by a network of interacting proteins.
authors.affiliation: Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Jaeschke
authors.forename: Maria
authors.initials: M
authors.lastname: Karasarides
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Ventura
authors.forename: Anka
authors.initials: A
authors.lastname: Ehrhardt
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018095:Germ-Line Mutation; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: C479693:1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D011720:Pyrazoles; D011743:Pyrimidines; D048056:Mitogen-Activated Protein Kinase 9