Skip to main content
Article thumbnail
Location of Repository

Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-fos Serum Response Element

By Jae-Won Soh, Eun Hae Lee, Ron Prywes and I. Bernard Weinstein

Abstract

Protein kinase C (PKC) is a multigene family of enzymes consisting of at least 11 isoforms. It has been implicated in the induction of c-fos and other immediate response genes by various mitogens. The serum response element (SRE) in the c-fos promoter is necessary and sufficient for induction of transcription of c-fos by serum, growth factors, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). It forms a complex with the ternary complex factor (TCF) and with a dimer of the serum response factor (SRF). TCF is the target of several signal transduction pathways and SRF is the target of the rhoA pathway. In this study we generated dominant-negative and constitutively active mutants of PKC-α, PKC-δ, PKC-ɛ, and PKC-ζ to determine the roles of individual isoforms of PKC in activation of the SRE. Transient-transfection assays with NIH 3T3 cells, using an SRE-driven luciferase reporter plasmid, indicated that PKC-α and PKC-ɛ, but not PKC-δ or PKC-ζ, mediate SRE activation. TPA-induced activation of the SRE was partially inhibited by dominant negative c-Raf, ERK1, or ERK2, and constitutively active mutants of PKC-α and PKC-ɛ activated the transactivation domain of Elk-1. TPA-induced activation of the SRE was also partially inhibited by a dominant-negative MEKK1. Furthermore, TPA treatment of serum-starved NIH 3T3 cells led to phosphorylation of SEK1, and constitutively active mutants of PKC-α and PKC-ɛ activated the transactivation domain of c-Jun, a major substrate of JNK. Constitutively active mutants of PKC-α and PKC-ɛ could also induce a mutant c-fos promoter which lacks the TCF binding site, and they also induce transactivation activity of the SRF. Furthermore, rhoA-mediated SRE activation was blocked by dominant negative mutants of PKC-α or PKC-ɛ. Taken together, these findings indicate that PKC-α and PKC-ɛ can enhance the activities of at least three signaling pathways that converge on the SRE: c-Raf–MEK1–ERK–TCF, MEKK1-SEK1-JNK-TCF, and rhoA-SRF. Thus, specific isoforms of PKC may play a role in integrating networks of signal transduction pathways that control gene expression

Topics: Gene Expression
Publisher: American Society for Microbiology
Year: 1999
OAI identifier: oai:pubmedcentral.nih.gov:116060
Provided by: PubMed Central
Sorry, our data provider has not provided any external links therefore we are unable to provide a link to the full text.

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.