2007
DOI: 10.1096/fj.07-8650com
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MEK1 and MEK2 regulate distinct functions by sorting ERK2 to different intracellular compartments

Abstract: In this study, we provide novel insight into the mechanism of how ERK2 can be sorted to different intracellular compartments and thereby mediate different responses. MEK1-activated ERK2 accumulated in the nucleus and induced proliferation. Conversely, MEK2-activated ERK2 was retained in the cytoplasm and allowed survival. Localization was a determinant for ERK2 functions since MEK1 switched from providing proliferation to be a mediator of survival when ERK2 was routed to the cytoplasm by the attachment of a nu… Show more

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Cited by 42 publications
(43 citation statements)
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“…Finally, MAP2K1 and MAP2K2 act at different steps during the cell cycle: MAP2K1 provides proliferative signals whereas MAP2K2 induces growth arrest at the G1/S boundary (Ussar and Voss, 2004). The role of MAP2K1 in proliferation seems to depend on its ability to translocate MAPK1 to the nucleus following MAP2K1 Thr292 and Ser298 phosphorylation (Skarpen et al, 2007). Altogether these data support a model in which the transduction of specific signals transits via distinct protein kinase isoforms through the ERK/MAPK cascade (Acharya et al, 1998).…”
Section: Introductionsupporting
confidence: 53%
See 1 more Smart Citation
“…Finally, MAP2K1 and MAP2K2 act at different steps during the cell cycle: MAP2K1 provides proliferative signals whereas MAP2K2 induces growth arrest at the G1/S boundary (Ussar and Voss, 2004). The role of MAP2K1 in proliferation seems to depend on its ability to translocate MAPK1 to the nucleus following MAP2K1 Thr292 and Ser298 phosphorylation (Skarpen et al, 2007). Altogether these data support a model in which the transduction of specific signals transits via distinct protein kinase isoforms through the ERK/MAPK cascade (Acharya et al, 1998).…”
Section: Introductionsupporting
confidence: 53%
“…Following gene duplication, decreased selection pressure can sometimes allow production of proteins with novel function or expression profile resulting in partial redundancy among gene family members. The biochemical properties of MAP2K1 and MAP2K2 proteins suggest that these two enzymes have evolved to be differentially utilized (Skarpen et al, 2007;Ussar and Voss, 2004). If the shared function of duplicated genes becomes unequally distributed between gene copies, unequal redundancy among the gene family members may result, as observed for the Erk/Map2k gene family, where the Map2k2 gene deletion does not cause any phenotype but enhances the Map2k1 placenta defects in a unique manner.…”
Section: Map2k2mentioning
confidence: 99%
“…Many studies suggest that both ERK1 and ERK2 compete for upstream mitogen-activated protein kinase kinases (MEK1/2) and other substrates (11). Moreover, the intensity and duration of ERK signaling, intracellular compartmentalization of phosphorylated (activated) ERKs (12), substrate specificity, and downstream consequences of ERK signaling, including activation of selected transcription factors, may determine phenotypic and functional cell outcomes (13,14). Activation of these cascades by asbestos fibers may play a role in initial cell injury, as well as compensatory mesothelial cell proliferation that favors survival of genetically altered cells in carcinogenesis.…”
mentioning
confidence: 99%
“…There are also studies that indicate MEK1 and MEK2 perform specific functions in hepatocytes. MEK2 mediates survival, whereas MEK1 is involved in proliferation (18). In the present study, we knocked down MEK1 and MEK2 expression to examine their functions in the progression of pancreatic cancer.…”
Section: Discussionmentioning
confidence: 98%