Journal of Biological Chemistry
Volume 276, Issue 44, 2 November 2001, Pages 40687-40692
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GLYCOBIOLOGY AND EXTRACELLULAR MATRICES
Decorin-mediated Signal Transduction in Endothelial Cells: INVOLVEMENT OF Akt/PROTEIN KINASE B IN UP-REGULATION OF p21WAF1/CIP1 BUT NOT p27KIP1*

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Endothelial cells undergoing angiogenesis express decorin, a small multifunctional proteoglycan. We have shown that decorin is causally involved in the formation of capillary-like structures and a decrease in apoptosis in endothelial cells cultured in a collagen lattice. Here we investigate signal transduction pathways mediating the effects of decorin. Reverse transcription-polymerase chain reaction demonstrated that p21 and p27, two inhibitors of cyclin-dependent kinases, were up-regulated by decorin induction. Decorin also increased protein levels of p21 and caused its translocation into the nucleus. p21 synthesis started 6 h after decorin addition and reached a plateau after 18 h, while cyclin A, which was also induced, peaked at 12 h and declined below basal levels within 24 h. These effects were mediated by the Akt/protein kinase B pathway. Akt phosphorylation at Thr-308 increased 4-fold and at Ser-473 1.4-fold within 10 min after decorin addition. Overexpression of dominant negative Akt inhibited the decorin-mediated induction of p21 and cyclin A, but had no effect on p27. These results show that decorin is a signaling molecule in sprouting endothelial cells where it acts via different pathways, one of them involving Akt/protein kinase B.

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Published, JBC Papers in Press, August 23, 2001, DOI 10.1074/jbc.M105426200

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This work was supported by the Deutsche Forschungsgemeinschaft (SFB 293, Project A7, SFB 396, Project A6).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.