Applying chemical genetics to mice, Roger Davis at University of Massachusetts Medical School and the Howard Hughes Medical Institute, and colleagues found that JNK2 promotes phosphorylation and activation of cJun.
"Based on the knockout approach, it had been concluded that JNK2 is a negative regulator of cJun and cell proliferation whereas JNK1 promotes this process. [This contradicts] observations that both kinases phosphorylate the same sites in cJun. By introducing in mice a mutant form of JNK2 [that is] exquisitely sensitive to an otherwise inactive kinase inhibitor, the authors demonstrated that JNK2 promotes phosphorylation of cJun and cell proliferation.
This is a particularly vivid illustration that the interpretation of genetic experiments using traditional knockout approaches is often complicated by compensation. With a knockout, you eliminate an entire protein but with a chemical inhibition you are instead specifically inhibiting the enzymatic activity of the protein but the protein is still there. This study clarifies an important issue in the field so now the energy can be focused on the biological functions of the important signaling pathways to which JNK1 and 2 participate."
1. A. Jaeschke et al., "JNK2 is a positive regulator of the cJun transcription factor," Mol Cell, 23:899-911, Sept. 15, 2006.