Protein kinase C signaling and cell cycle regulation

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

A link between T cell proliferation and the protein kinase C (PKC) family of serine/threonine kinases has been recognized for about 30 years. However, despite the wealth of information on PKC-mediated control of T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in othersystems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s) and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks), cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1 -> S and/or G2 -> M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling inT cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCΘ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted inT cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in T cells.

Original languageEnglish (US)
Article numberArticle 423
JournalFrontiers in immunology
Volume3
Issue numberJAN
DOIs
StatePublished - Dec 1 2012

Fingerprint

Protein Kinase C
Cell Cycle
Cyclin D
Isoenzymes
T-Lymphocytes
cdc25 Phosphatases
Cyclins
Cyclin-Dependent Kinases
Protein-Serine-Threonine Kinases
Cell Proliferation

Keywords

  • Cell cycle
  • Cyclin
  • Cyclin-dependent kinase
  • Cyclin-dependent kinase inhibitor
  • Protein kinase C
  • Signal transduction
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Protein kinase C signaling and cell cycle regulation. / Black, Adrian R; Black, Jennifer D.

In: Frontiers in immunology, Vol. 3, No. JAN, Article 423, 01.12.2012.

Research output: Contribution to journalReview article

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abstract = "A link between T cell proliferation and the protein kinase C (PKC) family of serine/threonine kinases has been recognized for about 30 years. However, despite the wealth of information on PKC-mediated control of T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in othersystems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s) and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks), cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1 -> S and/or G2 -> M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling inT cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCΘ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted inT cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in T cells.",
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