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Smads (sma/mothers against decapentaplegic) are transcription factors, which can be phosphorylated in the carboxy terminal (pSmad2/3C) or in the structurally central linker region (pSmad2/3 L). Only receptor kinases such as Transforming Growth Factor (TGF)-β receptor (TGFBR1) can mediate carboxy terminal phosphorylation but multiple receptors, including TGFBR1 itself, can activate cytosolic serine/threonine kinases and mediate serine/threonine (S/T) linker region phosphorylation of Smad2/3. One important class of agents that can mediate Smad phosphorylation are the G protein coupled receptors (GPCRs) and their ligands and these agents can meditate both carboxy terminal and linker region phosphorylation. Linker region phosphorylation arises due to activation of kinases including those downstream of the transactivation of the EGFR and carboxy terminal Smad phosphorylation can occur as a result of the recently described activity of GPCRs, notably protease activated receptors (PAR)-1, to transactivate TGFBR1 leading to direct carboxy terminal Smad phosphorylation. This review will summarize the effects of GPCR-mediated receptor transactivation pathways on the phosphorylation of Smad2 linker region, as a better understanding of these pathways may provide new approaches for the identification of novel therapeutic agents.

In the past three decades, endothelin and endothelin receptor antagonists have received great scientific and clinical interest, leading to the publication of more than 27,000 scientific articles since its discovery. The Thirteenth International Conference on Endothelin (ET-13) was held on September 8-11, 2013, at Tokyo Campus of the University of Tsukuba in Japan. Close to 300 scientists from 25 countries from around the world came to Tokyo to celebrate the anniversary of the discovery of the endothelin peptide discovered 25 years ago at the University of Tsukuba. This article summarizes some of the highlights of the conference, the anniversary celebration ceremony, and particularly the participation of next generation of endothelin researchers in endothelin science and the anniversary celebration. As a particular highlight, next generation endothelin researchers wrote a haiku (a traditional form of Japanese poetry originating from consisting of no more than three short verses and 27 on, or Japanese phonetic units) to describe the magic of endothelin science which they presented to the conference audience at the anniversary ceremony. The text of each haiku - both in its original language together with the English translation - is part of this article providing in an exemplary fashion how poetry can be bridged with science. Finally, we give an outlook towards the next 25 years of endothelin research.