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

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

Author information

1
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States.
2
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, United States. Electronic address: mkontari@bidmc.harvard.edu.

Abstract

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

PMID:
25256404
PMCID:
PMC4339543
DOI:
10.1016/j.semcdb.2014.09.013
[Indexed for MEDLINE]
Free PMC Article

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