Protein kinase A and local signaling in cancer

Biochem J. 2024 Nov 20;481(22):1659-1677. doi: 10.1042/BCJ20230352.

Abstract

Protein kinase A (PKA) is a basophilic kinase implicated in the modulation of many cell-signaling and physiological processes. PKA also contributes to cancer-relevant events such as growth factor action, cell cycle control, cell migration and tumor metabolism. Germline and somatic mutations in PKA, gene amplifications, and chromosome rearrangements that encode kinase fusions, are linked to a growing number of malignant neoplasms. Mislocalization of PKA by exclusion from A-Kinase Anchoring Protein (AKAP) signaling islands further underlies cancer progression. This article highlights the influence of AKAP signaling and local kinase action in selected hallmarks of cancer. We also feature the utility of kinase inhibitor drugs as frontline and future anti-cancer therapies.

Keywords: A Kinase Anchoring Proteins; cancer; fibrolamellar carcinoma; mislocalization; protein kinase A.

Publication types

  • Review

MeSH terms

  • A Kinase Anchor Proteins* / genetics
  • A Kinase Anchor Proteins* / metabolism
  • Animals
  • Cyclic AMP-Dependent Protein Kinases* / genetics
  • Cyclic AMP-Dependent Protein Kinases* / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / enzymology
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction*

Substances

  • Cyclic AMP-Dependent Protein Kinases
  • A Kinase Anchor Proteins
  • Protein Kinase Inhibitors