Editors' ChoiceScaffold Proteins

JIP1 Potentiates JNK Activation

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Science's STKE  25 Sep 2001:
Vol. 2001, Issue 101, pp. tw342
DOI: 10.1126/stke.2001.101.tw342

The JNK signaling pathway is activated when cells such as neurons are exposed to environmental stress. The JIP proteins are likely to act in this pathway because they bind to JNK, as well as to upstream activators of JNK. A report from Whitmarsh et al. now strengthens the argument that JIPs are scaffolding proteins that coordinate the formation of a JNK-activating module. JIP1 localized to the cell body and to the growth-cone tips of extended neurites in unstimulated murine hippocampal neurons, but upon exposure to various stress stimuli, JIP1 relocalized to the perinuclear region where activated JNK was also found. Neurons from a JIP1-null mouse did not demonstrate stress-induced JNK activation or apoptosis, demonstrating that JIP is required for JNK activation in vivo. Because JIP1 was isolated in a complex with kinesin from mouse brain tissue, the authors speculate that JIP translocation may involve cellular motor proteins. Such a transport mechanism may facilitate signal transduction from the cell surface to the nucleus.

A. Whitmarsh, C.-Y. Kuan, N. J. Kennedy, N. Kelkar, T. F. Haydar, J. P. Mordes, M. Appel, A. A. Rossini, S. N. Jones, R. A. Flavell, P. Rakic, R. J. Davis, Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev. 15: 2421-2432 (2001). [Abstract] [Full Text]