The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease

Semin Cell Dev Biol. 2015 Jan;37:73-81. doi: 10.1016/j.semcdb.2014.09.013. Epub 2014 Sep 22.


Congenital heart disease is the most common human developmental disorder, affecting ∼1:100 newborns, and is the primary cause of birth-defect related deaths worldwide. As a major regulator of receptor tyrosine kinase (RTK), cytokine and G-protein coupled receptor signaling, the non-receptor protein tyrosine phosphatase SHP2 plays a critical role in normal cardiac development and function. Indeed, SHP2 participates in a wide variety of cellular functions, including proliferation, survival, differentiation, migration, and cell-cell communication. Moreover, human activating and inactivating mutations of SHP2 are responsible for two related developmental disorders called Noonan and LEOPARD Syndromes, respectively, which are both characterized, in part, by congenital heart defects. Structural, enzymologic, biochemical, and SHP2 mouse model studies have together greatly enriched our knowledge of SHP2 and, as such, have also uncovered the diverse roles for SHP2 in cardiac development, including its contribution to progenitor cell specification, cardiac morphogenesis, and maturation of cardiac valves and myocardial chambers. By delineating the precise mechanisms by which SHP2 is involved in regulating these processes, we can begin to better understand the pathogenesis of cardiac disease and find more strategic and effective therapies for treatment of patients with congenital heart disorders.

Keywords: Cardiac development; Congenital heart disease; Myocardium; PTPN11; Phosphatase; SHP2.

Publication types

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

MeSH terms

  • Animals
  • Cell Survival
  • Heart / embryology
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / metabolism
  • Humans
  • Mutation
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism


  • Protein Tyrosine Phosphatase, Non-Receptor Type 11