CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway.

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 [(3)H]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 G(1)/G(o) to S phase.

authors

Torres-Marquez E,Sinnett-Smith J,Guha S,Kui R,Waldron RT,Rey O,Rozengurt E

doi

10.1016/j.bbrc.2009.11.002

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

63-8

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)02157-3

journal_volume

391

pub_type

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