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CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway |
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| Authors: | Eugenia Torres-Marquez James Sinnett-Smith Robert Kui Osvaldo Rey |
| Institution: | a Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, CURE: Digestive Diseases Research Center and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA b Biochemistry Department School of Medicine, UNAM, DF 45010, Mexico c Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA |
| Abstract: | Recently, CID755673 was reported to act as a highly selective inhibitor of protein kinase D (PKD). In the course of experiments using CID755673, we noticed that it exerted unexpected stimulatory effects on 3H]thymidine incorporation and cell cycle progression in Swiss 3T3 cells stimulated by bombesin, a Gq-coupled receptor agonist, phorbol 12,13-dibutyrate (PDBu), a biologically active tumor promoting phorbol ester and epidermal growth factor (EGF). These stimulatory effects could be dissociated from the inhibitory effect of CID755673 on PKD activity, since enhancement of DNA synthesis was still evident in cells with severely down-regulated PKD1 after transfection of siRNA targeting PKD1. A major point raised by our study is that CID755673 can not be considered a specific inhibitor of PKD and it should be used with great caution in experiments attempting to elucidate the role of PKD family members in cellular regulation, particularly cell cycle progression from G1/Go to S phase. |
| Keywords: | Swiss 3T3 cells PDGF PKD knock down Cell cycle DNA synthesis |
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