The tumor promoter-activated protein kinase Cs are a system for regulating filopodia

Carol A. Heckman, Pratima Pandey, Marilyn L. Cayer, Tania Biswas, Zhong-Yin Zhang, Nancy S. Boudreau

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Different protein kinase C (PKC) isoforms have distinct roles in regulating cell functions. The conventional (α, β, γ) and novel (δ, ɛ, η, θ) classes are targets of phorbol ester tumor promoters, which are surrogates of endogenous second messenger, diacylglycerol. The promoter-stimulated disappearance of filopodia was investigated by use of blocking peptides (BPs) that inhibit PKC maturation and/or docking. Filopodia were partially rescued by a peptide representing PKC ɛ hydrophobic sequence, but also by a myristoylated PKC α/β pseudosubstrate sequence, and an inhibitor of T-cell protein tyrosine phosphatase (TC-PTP). The ability to turn over filopodia was widely distributed among PKC isoforms. PKC α and η hydrophobic sequences enhanced filopodia in cells in the absence of tumor promoter treatment. With transcriptional knockdown of PKC α, the content of PKC ɛ predominated over other isoforms. PKC ɛ could decrease filopodia significantly in promoter-treated cells, and this was attributed to ruffling. The presence of PKC α counteracted the PKC ɛ-mediated enhancement of ruffling. The results showed that there were two mechanisms of filopodia downregulation. One operated in the steady-state and relied on PKC α and η. The other was stimulated by tumor promoters and relied on PKC ɛ. Cycles of protrusion and retraction are characteristic of filopodia and are essential for the cell to orient itself during chemotaxis and haptotaxis. By suppressing filopodia, PKC ɛ can create a long-term “memory” of an environmental signal that may act in nature as a mnemonic device to mark the direction of a repulsive signal.

Original languageEnglish (US)
Pages (from-to)297-314
Number of pages18
JournalCytoskeleton
Volume74
Issue number8
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Keywords

  • adhesion
  • cancer
  • contact inhibition
  • protrusions
  • signaling

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The tumor promoter-activated protein kinase Cs are a system for regulating filopodia'. Together they form a unique fingerprint.

  • Cite this

    Heckman, C. A., Pandey, P., Cayer, M. L., Biswas, T., Zhang, Z-Y., & Boudreau, N. S. (2017). The tumor promoter-activated protein kinase Cs are a system for regulating filopodia. Cytoskeleton, 74(8), 297-314. https://doi.org/10.1002/cm.21373