JNK2 is a positive regulator of the cJun transcription factor.
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.
Jaeschke
Anja
A
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Karasarides
Maria
M
Ventura
Juan-Jose
JJ
Ehrhardt
Anka
A
Zhang
Chao
C
Flavell
Richard A
RA
Shokat
Kevan M
KM
Davis
Roger J
RJ
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
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