Novel Betacellulin Derivatives

Abstract

Betacellulin (BTC) is a member of the epidermal growth factor family. It has two biological activities: mitogenic activity in fibroblasts and vascular smooth muscle cells, and differentiation activity for the differentiation of pancreatic acinar AR42J cells into insulinsecreting cells. The previous finding that recombinant BTC promotes the neogenesis of ␤-cells in a mouse model supports the possibility that BTC is a therapeutic protein. However, the mitogenic activity of BTC may not be needed for differentiation into ␤-cells and may cause a side effect in clinical use. We prepared several derivatives of BTC to segregate the two activities, to decrease the mitogenic activity, and to maintain the differentiation activity. We succeeded in obtaining BTC derivatives segregated by the two biological activities by preparing truncated-type derivatives. A derivative of BTC, BTC24 -76, with a truncated N-terminal 23 amino acids and C-terminal 4 amino acids, was 2.5-fold more active in differentiation and had one-tenth of the mitogenic activity. The derivatives described in the present study should be helpful in future applications as therapeutic proteins and in basic research for discovery of a BTCspecific receptor.

Oxylipin Signaling: A Distinct Role for the Jasmonic Acid Precursor cis-(+)-12-Oxo-Phytodienoic Acid (cis-OPDA)

“…A third branch of the oxylipin biosynthetic pathway originating from plastidial hydroperoxides originates through the activity of divinyl ether synthases that produce divinyl ether oxylipins which have also been shown to play a role in plant defense in a number of systems (Weber et al, 1999; Itoh and Howe, 2001). However, Eschen-Lippold et al (2010) have more recently reported that oxylipins resulting from the action of divinyl ether synthase are not required for the R -gene-mediated resistance in potato.…”