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Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine of key importance for controlling embryogenesis and tissue homeostasis. How TGF-beta signals are attenuated and terminated is not well understood. Here, we show that TMEPAI, a direct target gene of TGF-beta signaling, antagonizes TGF-beta signaling by interfering with TGF-beta type I receptor (TbetaRI)-induced R-Smad phosphorylation. TMEPAI can directly interact with R-Smads via a Smad interaction motif. TMEPAI competes with Smad anchor for receptor activation for R-Smad binding, thereby sequestering R-Smads from TbetaRI kinase activation. In mammalian cells, ectopic expression of TMEPAI inhibited TGF-beta-dependent regulation of plasminogen activator inhibitor-1, JunB, cyclin-dependent kinase inhibitors, and c-myc expression, whereas specific knockdown of TMEPAI expression prolonged duration of TGF-beta-induced Smad2 and Smad3 phosphorylation and concomitantly potentiated cellular responsiveness to TGF-beta. Consistently, TMEPAI inhibits activin-mediated mesoderm formation in Xenopus embryos. Therefore, TMEPAI participates in a negative feedback loop to control the duration and intensity of TGF-beta/Smad signaling.

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There have been numerous reports showing that space weather affects power grids through a geomagnetically induced current (GIC). Generally, power grids consist of power lines connected to transformers, of which neutral points are directly grounded. The GIC flows into those transformers through the neutral points if geomagnetic variations cause a ground level potential. These currents can damage power grids, especially transformers. It has been tacitly assumed, however, that the effect of the GIC is minor in Japan because of the country's location at geomagnetically lower latitudes. To examine the GIC effect in Japan, we conducted approximately 2 years of GIC measurements in Hokkaido, Japan. It is found that GICs associated with substorms can be detected in Japan even at the solar minimum although intense GICs do occur mostly during geomagnetic storms. Temporal variations of GICs show high correlation with geomagnetic field variations, rather than time derivatives of the geomagnetic field.

No abstract