PRKX critically regulates endothelial cell proliferation, migration, and vascular-like structure formation

Dev Biol. 2011 Aug 15;356(2):475-85. doi: 10.1016/j.ydbio.2011.05.673. Epub 2011 Jun 12.

Abstract

Angiogenesis is a fundamental step in several important physiological events and pathological conditions including embryonic development, wound repair, tumor growth and metastasis. PRKX was identified as a novel type-I cAMP-dependent protein kinase gene expressed in multiple developing tissues. PRKX has also been shown to be phylogenetically and functionally distinct from PKA. This study presents the first evidence that PRKX stimulates endothelial cell proliferation, migration, and vascular-like structure formation, which are the three essential processes for angiogenesis. In contrast, classic PKA demonstrated an inhibitory effect on endothelia vascular-like structure formation. Our findings suggest that PRKX is an important protein kinase engaged in the regulation of angiogenesis and could play critical roles in various physiological and pathological conditions involving angiogenesis. PRKX binds to Pin-1, Magi-1 and Bag-3, which regulate cell proliferation, apoptosis, differentiation and tumorigenesis. The interaction of PRKX with Pin-1, Magi-1 and Bag-3 could contribute to the stimulating role of PRKX in angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Endothelial Cells / physiology*
  • Humans
  • Mice
  • Neovascularization, Physiologic*
  • Protein Serine-Threonine Kinases / physiology*
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Vascular Endothelial Growth Factor A
  • PRKX protein, human
  • PRKX protein, mouse
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases