Editors' ChoiceCell Biology

Signaling in Time and Place

Science Signaling  05 Aug 2008:
Vol. 1, Issue 31, pp. ec276
DOI: 10.1126/scisignal.131ec276

Proteins that participate in biological regulatory mechanisms are often assembled into large complexes within which various signaling molecules interact to propagate a biochemical signal. Matsuzawa et al. characterize such a complex of proteins assembled at the activated receptor CD40 (a member of the tumor necrosis factor receptor family) on the cell surface. The complex formed at the cell surface within a few minutes after binding of ligand to the receptor but after 30 minutes had moved to the cytoplasm. Surprisingly, activation of mitogen-activated protein kinases (MAPKs) JNK and p38 and of the MAPK kinase MEKK1 was only detected once the complex left the receptor and moved into the cytosol. Degradation of the adaptor protein TRAF3 was required to initiate release of the complex from CD40. Other receptors may also use such a mechanism to specify the time and place at which signaling proteins are activated in response to receptor stimulation.

A. Matsuzawa, P.-H. Tseng, S. Vallabhapurapu, J.-L. Luo, W. Zhang, H. Wang, D. A. A. Vignali, E. Gallagher, M. Karin, Essential cytoplasmic translocation of a cytokine receptor–assembled signaling complex. Science 321, 663-668 (2008). [Abstract] [Full Text]

A. G. Eliopoulos, "Make and brake" in signaling. Science 321, 648-649 (2008). [Summary] [Full Text]