Sci. STKE, 6 November 2001
Protein Phosphatases Sequestering and Deactivating MAP Kinases
Volmat et al. studied how signals are terminated by observing the inactivation of mitogen-associated protein kinases (MAPKs). They found that the stimulation of cells with various factors (mitogenic or not) promoted the nuclear relocalization of the phosphorylated MAPKs extracellular-regulated kinase 1 (ERK1) and ERK2, but that long-term stimulation, on the order of several hours, actually led to a large accumulation of unphosphorylated ERK1 and ERK2 in the nucleus. Subsequent dephosphorylation of the activated, nuclear MAPKs required the de novo synthesis of protein phosphatases. Although the data suggest that the phosphatases involved were the MAPK-specific phosphatases, MKP1 and MKP2, definitive proof remains to be provided. However, microinjection of a peptide from the p90 ribosomal S6 protein kinase (p90rsk) COOH-terminus into cell nuclei, previously shown to disrupt the interaction of MAPKs and MKPs, did inhibit the dephosphorylation of nuclear-accumulated MAPKs, suggesting that MKPs were involved in the nuclear inactivation of MAPKs. Because previous reports indicated that nuclear phosphatases can also function to tether, and thus sequester, unphosphorylated MAPKs such as p38 MAPK and JNK3, the authors suggest that MKP1 and MKP2 might extinguish ERK1- and ERK2-dependent signaling through dephosphorylation and tethering in the nucleus.
V. Volmat, M. Camps, S. Arkinstall, J. Pouysségur, P. Lenormand, The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases. J. Cell Sci. 114, 3433-3443 (2001). [Online Journal]
Citation: Sequestering and Deactivating MAP Kinases. Sci. STKE 2001, tw413 (2001).
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