ROCKs cause SHP-wrecks and broken hearts

Small GTPases. Oct-Dec 2012;3(4):209-12. doi: 10.4161/sgtp.20960. Epub 2012 Aug 3.

Abstract

During embryogenesis, the heart is one of the first organs to develop. Its formation requires a complex combination of migration of cardiac precursors to the ventral midline coupled with the fusion of these cardiogenic fields and subsequent cellular reorganization to form a linear heart tube. A finely controlled choreography of cell proliferation, adhesion, contraction and movement drives the heart tube to loop and subsequently septate to form the four-chambered mammalian heart we are familiar with. Defining how this plethora of cellular processes is controlled both spatially and temporally is a scientific feat that has fascinated researchers for decades. Unfortunately, the complex nature of this organ's development also makes it a prime target for mutation-induced malformation, as evidenced by the multitude of prevalent congenital heart disorders identified that afflict up to 1% of the population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Heart Defects, Congenital / drug therapy
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / metabolism*
  • Humans
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism*

Substances

  • Protein Kinase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • rho-Associated Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • fasudil